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Triple Negative Breast Cancer (TNBC)

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(@j)
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@rosaleend @laika @chris48 @jens

There's an issue with the formatting so I'm starting this new thread before it gets worse.

Links to previous threads:

TNBC / testing strategies in a NED situation
https://www.cancertreatmentsresearch.com/community/breast-cancer/tnbc-testing-strategies-in-a-ned-situation/

TNBC reoccurrence mets to skin inoperable tumour In right breast and left lymph node involved
https://www.cancertreatmentsresearch.com/community/breast-cancer/tnbc-reoccurrence-mets-to-skin-inoperable-tumour-in-right-breast-and-left-lymph-node-involved/#post-6267


   
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(@j)
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Posts: 2160
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Glucocorticoids promote breast cancer metastasis

https://www.nature.com/articles/s41586-019-1019-4

"We also find that the stress hormone pathway is an effective inducer of colonization and death in mouse models, and that ROR1 ablation prevents the deleterious effect of GR activation. Our data also reveal that GR
activation decreases the efficacy of paclitaxel. Corticosteroids such as dexamethasone are widely used in the treatment of breast cancer to combat the side effects of chemotherapy and to treat symptoms related
to advanced cancer. Given that cancer cell dissemination has already occurred by the time of surgical resection of the primary tumour in a substantial number of patients with breast cancer14,30, and that GR
activation fosters colonization at the distant sites, our results suggest that caution is needed when administering corticosteroids to patients. "

Breast Cancer With Brain Metastases: Perspective From a Long-Term Survivor
Christopher P. Kofron, PhD and Angela Chapman, PhD
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947880/

" In addition, the patient supplemented with numerous other drugs and substances that are reported in scientific publications to have antitumor properties, including artemisinin,12,13 aspirin,14,15 cannabidiol,16 chloroquine,17-19 doxycycline,20 flaxseed oil,21 hydroxychloroquine,18,19 indole-3-carbinol,22,23 melatonin,24,25 nanocurcumin,22,26 omega-3 fish oil,27 pterostilbene,28,29 quercetin,22,30 resveratrol,14,22 turkey tail mushroom (Trametes [Coriolus] versicolor),31,32 and vitamin D3. 24,33,34"


   
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(@j)
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Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass. Spinelli JB, Yoon H, Ringel AE, Jeanfavre S, Clish CB, Haigis MCScience. 2017 Nov 17;358(6365):941-946. doi: 10.1126/science.aam9305. Epub 2017 Oct 12. PMID: 29025995; PMCID: PMC5748897.

Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells. Warkad, M.S., Kim, CH., Kang, BG. et al. Sci Rep 11, 14002 (2021). https://doi.org/10.1038/s41598-021-93270-0

Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression
Antonio F. Santidrian AND Akemi Matsuno-Yagi AND Melissa Ritland AND Byoung B. Seo AND Sarah E. LeBoeuf AND Laurie J. Gay AND Takao Yagi AND Brunhilde Felding-Habermann
https://doi.org/10.1172/JCI64264

Rapamycin Plus Doxycycline Combination Affects Growth Arrest and Selective Autophagy-Dependent Cell Death in Breast Cancer Cells. Dankó T, Petővári G, Sztankovics D, Moldvai D, Raffay R, Lőrincz P, Visnovitz T, Zsiros V, Barna G, Márk Á, Krencz I, Sebestyén A.Int J Mol Sci. 2021 Jul 27;22(15):8019. doi: 10.3390/ijms22158019. PMID: 34360785; PMCID: PMC8347279.

In Vivo Xenograft Model.
Rapamune (Pfizer – Budapest, Hungary; active ingredient: rapamycin) by gavage at 3 mg/kg body weight; (3) doxycycline (Merck-Sigma-Aldrich)—5 mg/kg body weight.
The treatments were administered three times per week for 3 weeks.
The rapamycin + doxycycline combination was more effective than traditional chemotherapy—doxorubicin in ZR75.1 Breast Cancer Cells.
R + D exhibit synergistic growth inhibitory effects in ZR75.1 and additive inhibition in MDA-MB-231 cells.

Study on the effect of ursolic acid on MMPs and antimetastatic activity in TNBC cells
https://doi.org/10.1016/j.phyplu.2022.100265

EGCG Inhibits Adipose-Derived Mesenchymal Stem Cells Differentiation into Adipocytes and Prevents a STAT3-Mediated Paracrine Oncogenic Control of Triple-Negative Breast Cancer Cell Invasive Phenotype
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998295/

MYCL promotes the progression of triple‑negative breast cancer by activating the JAK/STAT3 pathway
https://www.spandidos-publications.com/10.3892/or.2022.8418
pharmacological inhibition of the PI3K/AKT/mTOR pathway markedly decreased Myc level and exhibited remarkable therapeutic efficacy in Myc-driven cancers
insulin upregulates the expression of c-Myc

Reverse engineering of triple-negative breast cancer cells for targeted treatment
https://www.sciencedirect.com/science/article/abs/pii/S0378512217308526

Taurine induces the apoptosis of breast cancer cells by regulating apoptosis-related proteins of mitochondria
https://pubmed.ncbi.nlm.nih.gov/25395275/

Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633285/

Kaempferol as a Potential PAK4 Inhibitor in Triple Negative Breast Cancer: Extra Precision Glide Docking and Free Energy Calculation
https://www.researchgate.net/publication/335381456_Kaempferol_as_a_Potential_PAK4_Inhibitor_in_Triple_Negative_Breast_Cancer_Extra_Precision_Glide_Docking_and_Free_Energy_Calculation

Drug-repositioning screening identified piperlongumine as a direct STAT3 inhibitor with potent activity against breast cancer
https://pubmed.ncbi.nlm.nih.gov/24681959/

Targeting hypoxia-inducible factor-1alpha: A new strategy for triple-negative breast cancer therapy
https://www.sciencedirect.com/science/article/pii/S0753332222012501

Lactobacilli Modulate Hypoxia-Inducible Factor (HIF)-1 Regulatory Pathway in Triple Negative Breast Cancer Cell Line
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988423/

Natural Compounds Regulate Glycolysis in Hypoxic Tumor Microenvironment
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317583/

Identification of Natural Compounds as Inhibitors of Pyruvate Kinase M2 for Cancer Treatment
https://pubmed.ncbi.nlm.nih.gov/36296707

Mitochondrial Protein UCP1 Inhibits the Malignant Behaviors of Triple-negative Breast Cancer through Activation of Mitophagy and Pyroptosis
https://pubmed.ncbi.nlm.nih.gov/35541900/

Browning Effects of a Chronic Pterostilbene Supplementation in Mice Fed a High-Fat Diet
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862528/

Naringenin Promotes Thermogenic Gene Expression in Human White Adipose Tissue
https://onlinelibrary.wiley.com/doi/full/10.1002/oby.22352

Exploring the molecular targets and mechanisms of [10]-Gingerol for treating triple-negative breast cancer using bioinformatics approaches, molecular docking, and in vivo experiments
https://cdn.amegroups.cn/journals/pbpc/files/journals/3/articles/58709/public/58709-PB12-7254-R3.pdf

Diallyl trisulfides, a natural histone deacetylase inhibitor, attenuate HIF-1α synthesis, and decreases breast cancer metastasis
https://onlinelibrary.wiley.com/doi/abs/10.1002/mc.22686

Compounds from Natural Sources as Protein Kinase Inhibitors
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698043/

Gingers and Their Purified Components as Cancer Chemopreventative Agents
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719158/

The “Yin and Yang” of Natural Compounds in Anticancer Therapy of Triple-Negative Breast Cancers
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209965/

Apigenin Induces Apoptosis and Blocks Growth of Medroxyprogesterone Acetate-Dependent BT-474 Xenograft Tumors
https://link.springer.com/article/10.1007/s12672-012-0114-x

Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF-??B signaling
https://www.researchgate.net/publication/26817769_Matrine_suppresses_breast_cancer_cell_proliferation_and_invasion_via_VEGF-Akt-NF-B_signaling

Carbonic Anhydrase Expression in TNBC Breast Cancer Cells and Human Tumor Grafts
https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.29.1_supplement.725.14

Ornithine and breast cancer: a matched case–control study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511971/

Identification for antitumor effects of tramadol in a xenograft mouse model using orthotopic breast cancer cells
https://www.nature.com/articles/s41598-021-01701-9

The therapeutic potential of targeting tryptophan catabolism in cancer
https://www.nature.com/articles/s41416-019-0664-6

Highly Metastatic Subpopulation of TNBC Cells Has Limited Iron Metabolism and Is a Target of Iron Chelators https://pubmed.ncbi.nlm.nih.gov/36672419/
Naringin is a promising natural compound for therapy of iron-overload disorders "We found that naringin is able to decrease serum iron level in an effective manner, even more potent than the gold standard, desferal."
https://www.scielo.br/j/bjps/a/QCq7fk6CszPnvHNr7RfFWCG/?format=pdf&lang=en

ROR activation by Nobiletin enhances antitumor efficacy via suppression of IκB/NF-κB signaling in triple-negative breast cancer
https://www.nature.com/articles/s41419-022-04826-5

Aurora Kinase A and Bcl-xL Inhibition Suppresses Metastasis in Triple-Negative Breast Cancer
https://pubmed.ncbi.nlm.nih.gov/36077449/

Drivers and suppressors of triple-negative breast cancer
https://www.pnas.org/doi/10.1073/pnas.2104162118
Structural activity relationship of flavonoids with estrogen-related receptor gamma https://core.ac.uk/download/pdf/82376813.pdf

GPER1 promotes estrogen receptor-negative breast cancer cell migration and invasion via non-genomic activation of c-Src/NF-κB/focal adhesion kinase cascade
https://journals.lww.com/jbioxresearch/Fulltext/2018/09000/GPER1_promotes_estrogen_receptor_negative_breast.1.aspx

Chrysin inhibits metastatic potential of human triple-negative breast cancer cells by modulating matrix metalloproteinase-10, epithelial to mesenchymal transition, and PI3K/Akt signaling pathway
https://pubmed.ncbi.nlm.nih.gov/24122885/

Anti-cancer Effect of Apigenin on Human Breast Carcinoma MDA-MB-231 through Cell Cycle Arrest and Apoptosis
https://koreascience.kr/article/JAKO201912761598311.pdf

MAPK4 promotes triple negative breast cancer growth and reduces tumor sensitivity to PI3K blockade
https://www.nature.com/articles/s41467-021-27921-1

Mebendazole prevents distant organ metastases in part by decreasing ITGβ4 expression and cancer stemness
https://pubmed.ncbi.nlm.nih.gov/36578038/

Honokiol mediated inhibition of PI3K/mTOR pathway: A potential strategy to overcome immunoresistance in glioma, breast and prostate carcinoma without impacting T cell function
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795513/

miRNA-21 promotes proliferation and invasion of triple-negative breast cancer cells through targeting PTEN
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5375989/
The effect of hesperidin and luteolin isolated from Eriocephalus africanus on apoptosis, cell cycle and miRNA expression in MCF-7 https://www.tandfonline.com/doi/full/10.1080/07391102.2020.1833757

An FDA-Approved Antifungal, Ketoconazole, and Its Novel Derivative Suppress tGLI1-Mediated Breast Cancer Brain Metastasis by Inhibiting the DNA-Binding Activity of Brain Metastasis-Promoting Transcription Factor tGLI1
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9454738/

HTR1A Inhibits the Progression of Triple‐Negative Breast Cancer via TGF‐β Canonical and Noncanonical Pathways
"The combined treatment of HTR1A agonists with demethylation drugs may significantly improve patient survival."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036047/
Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: Novel anti-tumor mechanisms of Cannabidiol in breast cancer {ref}

Polyphenol-Rich Muscadine Grape Extract Reduces Triple Negative Breast Cancer Metastasis in Mice with Changes in the Gut Microbiome
https://assets.researchsquare.com/files/rs-384168/v1/3b066e44-2a82-4eda-ac2e-27ceac5a81d3.pdf

Blueberry Phytochemicals Inhibit Growth and Metastatic Potential of MDA-MB-231 Breast Cancer Cells Through Modulation of the Phosphatidylinositol 3-Kinase Pathway
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862148/
"The dose of blueberry in our in vivo study is equal to a fresh blueberry intake of 25 grams/kg. With a conversion to human dose (based on surface area) (49), this is equal to 2.03 g/kg human or 122 grams (4.3 oz) of fresh blueberries/day for a 60 kg person. A single serving of fresh blueberries is 6 oz. which is an attainable intake for the average person. Therefore, blueberry intake could be an important part of dietary cancer prevention strategies."

Identification of FOXM1 as a specific marker for triple‑negative breast cancer
https://pubmed.ncbi.nlm.nih.gov/30365046/

The exploration of contrasting pathways in Triple Negative Breast Cancer (TNBC)
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3939-4

Bioinformatics driven discovery of small molecule compounds that modulate the FOXM1 and PPARA pathway activities in breast cancer
https://www.nature.com/articles/s41397-022-00297-1
https://www.nature.com/articles/s41397-022-00297-1/tables/4

Exposure of breast cancer cells to hypoxia induces FAK phosphorylation/activation {ref}

Down-regulation of FOXM1 inhibits Focal Adhesion Kinase (FAK) activity in breast cancer cells {ref}

The Role of PPARs in Breast Cancer
https://pubmed.ncbi.nlm.nih.gov/36611922/

Down-regulation of c-MYC and hTERT gene expression in triple negative breast cancer
https://aacrjournals.org/cancerres/article/77/13_Supplement/1520/616968/Abstract-1520-Down-regulation-of-c-MYC-and-hTERT

Therapeutic Role of Tamoxifen for Triple-Negative Breast Cancer: Leveraging the Interaction Between ERβ and Mutant p53
https://academic.oup.com/oncolo/advance-article/doi/10.1093/oncolo/oyac281/7034511

Tamoxifen reverses epithelial–mesenchymal transition by demethylating miR-200c in triple-negative breast cancer cells
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3457-4

Modulatory effect of sodium butyrate on anticancer activity of abemaciclib in MDA-MB- 231 human breast cancer cells
https://assets.researchsquare.com/files/rs-1619486/v2/c6ab5cc6-a09f-4917-9379-12a2c6b07b2e.pdf?c=1656351870

Divergent effects of vitamins K1 and K2 on triple negative breast cancer cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481349/

ZHX2 promotes HIF1α oncogenic signaling in triple-negative breast cancer
https://elifesciences.org/articles/70412

Targeting hypoxia-inducible factor 1 (HIF-1) signaling with natural products toward cancer chemotherapy
https://www.nature.com/articles/s41429-021-00451-0

Emodin inhibits epithelial‑mesenchymal transition and metastasis of triple negative breast cancer via antagonism of CC‑chemokine ligand 5 secreted from adipocytes
https://www.spandidos-publications.com/10.3892/ijmm.2018.3638

The Effect of Different Probiotic Bacterial Strains on Ammonia (NH3) Production Levels
https://csef.usc.edu/History/2017/Projects/S1612.pdf
(Lactobacillus bulgaricus, Lactobacillus acidophilus, Bifidobacterium longum, Saccharomyces boulardii)

Shikonin inhibits triple-negative breast cancer-cell metastasis by reversing the epithelial-to-mesenchymal transition via glycogen synthase kinase 3β-regulated suppression of β-catenin signaling
https://pubmed.ncbi.nlm.nih.gov/31071331/

Targeting Tumor Acidosis and Regulatory T Cells Unmasks Anti-Metastatic Potential of Local Tumor Ablation in Triple-Negative Breast Cancer
https://www.mdpi.com/1422-0067/23/15/8479/htm

Curcumin-induced antitumor effects on triple-negative breast cancer patient-derived xenograft tumor mice through inhibiting salt-induced kinase-3 protein
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931023/

Synergies

https://synergiesforcancertreatments.blogspot.com/p/synergies.html
https://synergiesforcancertreatments.blogspot.com/2020/11/combination-of-natural-supplements-as.html

In vitro anticancer efficacy of a polyphenolic combination of Quercetin, Curcumin, and Berberine in triple-negative breast cancer (TNBC) cells
Akanksha Kashyap a, Sheikh Mohammad Umar, Arundhathi Dev J․R․, Mohini Mendiratta, Chandra Prakash Prasad
https://doi.org/10.1016/j.phyplu.2022.100265

Synergistic anticancer action of quercetin and curcumin against triple-negative breast cancer cell lines
https://onlinelibrary.wiley.com/doi/10.1002/jcp.27761

Vitamin B2 Sensitizes Cancer Cells to Vitamin-C-Induced Cell Death via Modulation of Akt and Bad Phosphorylation
https://pubmed.ncbi.nlm.nih.gov/26165392/

Enhanced Anticancer Effect of Adding Magnesium to Vitamin C Therapy: Inhibition of Hormetic Response by SVCT-2 Activation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940627/

Beta 2 Adrenergic Receptor Antagonist Propranolol and Opioidergic Receptor Antagonist Naltrexone Produce Synergistic Effects on Breast Cancer Growth Prevention by Acting on Cancer Cells and Immune Environment in a Preclinical Model of Breast Cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508249/

Zoledronate and Molecular Iodine Cause Synergistic Cell Death in Triple Negative Breast Cancer through Endoplasmic Reticulum Stress
https://pubmed.ncbi.nlm.nih.gov/27116040/

Synergistic inhibitory effects of genistein and tamoxifen on human dysplastic and malignant epithelial breast cells in vitro
https://pubmed.ncbi.nlm.nih.gov/11950489/

Synergistic inhibition of the growth of MDA‑MB‑231 cells in triple‑negative breast cancer by salinomycin combined with 17‑AAG (Tanespimycin) and its mechanism
https://www.spandidos-publications.com/10.3892/ol.2022.13258

Combined xanthorrhizol-curcumin exhibits synergistic growth inhibitory activity via apoptosis induction in human breast cancer cells MDA-MB-231
https://cancerci.biomedcentral.com/articles/10.1186/1475-2867-9-1

Computational pharmacogenomic screen identifies drugs that potentiate the anti-breast cancer activity of statins
https://www.nature.com/articles/s41467-022-33144-9

A combination of Calcitriol (the activated form of vitamin D3) and ketoconazole exhibit strong inhibitory effects
https://www.pnas.org/doi/10.1073/pnas.2104162118

Synergy of theophylline reduces necrotic effect of berberine, induces cell cycle arrest and PARP, HMGB1, Bcl-2 family mediated apoptosis in MDA-MB-231 breast cancer cells
https://www.sciencedirect.com/science/article/abs/pii/S0753332218329287

Combination treatment of bicalutamide and curcumin has a strong therapeutic effect on androgen receptor-positive triple-negative breast cancers
https://pubmed.ncbi.nlm.nih.gov/31917699/

Aspirin in combination with Letrozole or Olaparib induced apoptosis in estrogen receptor-positive T-47D & triple negative MDA-MB-231 breast cancer cell lines
https://aacrjournals.org/cancerres/article/80/16_Supplement/1441/641367/Abstract-1441-Aspirin-in-combination-with

Combinatorial therapy of Thymoquinone and Emodin synergistically enhances apoptosis, attenuates cell migration and reduces stemness efficiently in breast cancer
https://www.sciencedirect.com/science/article/abs/pii/S0304416520302075

Synergy between sublethal doses of shikonin and metformin fully inhibits breast cancer cell migration and reverses epithelial-mesenchymal transition
https://pubmed.ncbi.nlm.nih.gov/35525887/

Synergistic apoptotic effect of celecoxib and luteolin on breast cancer cells
https://www.spandidos-publications.com/10.3892/or.2012.2158

Anthocyanin and Gingerol Extracts Exhibit a Synergistic Effect to Inhibit the Proliferation of Caco-2, Hep G2, and HT-29 Cells in Vitro
"Strong synergism levels at high growth inhibitory effects suggest that the anthocyanin–gingerol combination has high potency for the inhibition of cancer cell growth."
https://pubs.acs.org/doi/abs/10.1021/acsfoodscitech.1c00029

Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1 / Journal of the Korean Cancer Association, 대한암학회지
https://search.bvsalud.org/gim/resource/pt/wpr-889762

Targeting carbonic anhydrase IX improves the anti-cancer efficacy of mTOR inhibitors
https://www.oncotarget.com/article/9134/text/

TNBC recurrence

"8 out of 13 initially triple-negative patients (61.5%) had a change to positive status of either ER, PR, or HER2".
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754865/

HER2+

Sirolimus and trastuzumab combination therapy for HER2-positive metastatic breast cancer after progression on prior trastuzumab therapy
https://pubmed.ncbi.nlm.nih.gov/25687356/

The mTOR Inhibitor Rapamycin Synergizes with a Fatty Acid Synthase Inhibitor to Induce Cytotoxicity in ER/HER2-Positive Breast Cancer Cells
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0097697

Successful Treatment of HER2-neu–positive Breast Cancer With Paclitaxel and Trastuzumab Supplemented With Turkey Tail Mushrooms and Community Support
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890094/

Trastuzumab enhances the anti-tumor effects of the histone deacetylase inhibitor sodium butyrate on a HER2-overexpressing breast cancer cell line
https://pubmed.ncbi.nlm.nih.gov/21887460/

Magnolol down-regulates HER2 gene expression, leading to inhibition of HER2-mediated metastatic potential in ovarian cancer cells.
https://europepmc.org/article/med/21757288

A combination of anti-HER2 and anti-PD-L1 therapy may have synergistic effects. {ref}

HER2 regulates HIF-2α and drives an increased hypoxic response in breast cancer
https://pubmed.ncbi.nlm.nih.gov/30670058/

Apigenin inhibits Hif1 and Hif2-alpha {ref}

Anthelminthic niclosamide inhibits tumor growth and invasion in cisplatin‑resistant human epidermal growth factor receptor 2‑positive breast cancer
https://www.spandidos-publications.com/10.3892/ol.2021.12927/abstract

Aspirin and atenolol enhance metformin activity against breast cancer by targeting both neoplastic and microenvironment cells
https://www.researchgate.net/publication/289504071_Aspirin_and_atenolol_enhance_metformin_activity_against_breast_cancer_by_targeting_both_neoplastic_and_microenvironment_cells

CCL2/CCR2 Regulates the Tumor Microenvironment in HER-2/neu-Driven Mammary Carcinomas in Mice
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165595
Sanguinarine Inhibition of TNF-α-Induced CCL2, IKBKE/NF-κB/ERK1/2 Signaling Pathway, and Cell Migration in Human Triple-Negative Breast Cancer Cells {study}

Targeting of PYK2 Synergizes with EGFR Antagonists in Basal-like TNBC and Circumvents HER3-Associated Resistance via the NEDD4–NDRG1 Axis
https://aacrjournals.org/cancerres/article/77/1/86/616041/Targeting-of-PYK2-Synergizes-with-EGFR-Antagonists

Dorsomorphin (Compound C) enhances the anticancer effect of aspirin in HER-2-positive breast cancer by regulating lipid metabolism in an AMPK-independent pathway
https://www.ijbs.com/v16p0583.htm

Apigenin Induces Apoptosis and Blocks Growth of Medroxyprogesterone Acetate-Dependent BT-474 Xenograft Tumors

"Our data clearly show that apigenin (50 mg/kg) inhibits progression and development of these xenograft tumors by inducing apoptosis, inhibiting cell proliferation, and reducing expression of Her2/neu. Moreover, apigenin reduced levels of vascular endothelial growth factor (VEGF) without altering blood vessel density"

Dose conversion: approx 300mg Apigenin in 75kg human. In the metformin study 240mg.

HER2+ breast cancer cells undergo apoptosis upon exposure to tannic acid released from remodeled cross-linked collagen type I
https://pubmed.ncbi.nlm.nih.gov/28877394/

CYP hydroxylase and sEH metabolites are most significantly elevated in ER−/PR−/HER2+ tumors {ref}

MMP-9 expression varies according to molecular subtypes of breast cancer
MMP-9 overexpression revealed itself as a startling feature of triple-negative and HER2-positive breast cancers
https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-14-609

ER+/PR+

Interactions Between Natural Products and Tamoxifen in Breast Cancer: A Comprehensive Literature Review
https://www.frontiersin.org/articles/10.3389/fphar.2022.847113/full

⚠ Vitamin C attenuates the cytotoxicity of tamoxifen. Vitamin C suppresses cell death in MCF-7 human breast cancer cells induced by tamoxifen.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930417/

⚠ Iodine stimulates estrogen receptor singling and its systemic level is increased in surgical patients due to topical absorption
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787473/

Combined Luteolin and Indole-3-Carbinol Synergistically Constrains ERα-Positive Breast Cancer by Dual Inhibiting Estrogen Receptor Alpha and Cyclin-Dependent Kinase 4/6 Pathway in Cultured Cells and Xenograft Mice
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123907/

Green tea increases the effectiveness of tamoxifen
https://aacrjournals.org/cancerres/article/65/9_Supplement/1223/523872/Green-tea-increases-the-effectiveness-of-tamoxifen

Grape Seed Procyanidins Inhibit the Growth of Breast Cancer MCF-7 Cells by Down-Regulating the EGFR/VEGF/MMP9 Pathway
https://journals.sagepub.com/doi/full/10.1177/1934578X21991691

Prevention of Bone Loss by Zoledronic Acid in Premenopausal Women Undergoing Adjuvant Chemotherapy Persist up to One Year following Discontinuing Treatment
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840866/

Modulating the Activity of Androgen Receptor for Treating Breast Cancer
https://www.mdpi.com/1422-0067/23/23/15342

Combined Luteolin and Indole-3-Carbinol Synergistically Constrains ERα-Positive Breast Cancer by Dual Inhibiting Estrogen Receptor Alpha and Cyclin-Dependent Kinase 4/6 Pathway in Cultured Cells and Xenograft Mice
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123907/

Case Reports

Case report of long-term survival with metastatic triple-negative breast carcinoma
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494386/

Long-Term Non-progression in Metastatic Breast Cancer Beyond 5 Years: Case Series and Review
https://link.springer.com/article/10.1007/s12609-021-00410-6

Long-Term Progression-Free Survival of Stage IV Triple Negative Breast Cancer Patient having Genetic Mutation with Variant of Uncertain Significance and Lung Metastasis: A Case Report Emphasizing Role of Ayurvedic Treatment
https://www.gavinpublishers.com/article/view/long-term-progression-free-survival-of-stage--iv-triple-negative-breast-cancer-patient-having-genetic-mutation-with-variant-of-uncertain--significance-and-lung-metastasis-a-case-report-emphasizing-role-of-ayurvedic-treatment

Breast Cancer With Brain Metastases: Perspective From a Long-Term Survivor Christopher P. Kofron, PhD and Angela Chapman, PhD
https://journals.sagepub.com/doi/pdf/10.1177/1534735419890017

Dose calculations

Estimation of dosages used in some of the studies mentioned above, using dose conversions between species. (based on 75kg person)

Metformin 760mg + Apigenin 243mg {ref}
Ketoconazole 200 mg tablets, 2 tablets orally TID + Calcitriol (0.5 mcg caplets) given in escalating doses, orally QD X3 consecutive days every week {ref}
Rapamycin 18mg + Doxycycline 30mg (3x/week for 21 days) {ref}
Doxycycline approx 350mg {ref}
Honokiol + Fluvastatin 20-80mg/d {ref}
Emodin (30- 60mg) {ref}
Magnolol (120 - 600mg) {ref | ref}
Quercetin approx 1300mg {ref}
Magnesium sulfate (approx 600mg) {ref}

To calculate the dose for a different weight e.g. 55kg

75kg → estimated dose e.g 760mg
÷75 → (760 ÷ 75)
1kg → 10,13mg
✕ 55 → (10,13 ✕ 55)
===============
55kg → approx 557mg

Diet

Divergent effects of vitamins K1 and K2 on triple negative breast cancer cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481349/
"To assess differential effects of vitamin K, TNBC cells were cultured in media supplemented with K1 or K2.
K1 treatment increased cell growth, and enhanced stemness and GLA-modified protein expression in TNBC lysates. Alternatively, lysates from cells exposed to vehicle, K2, or the VKOR antagonist, warfarin, did not express GLA-modified proteins. Further, K2 exposure reduced stemness and elicited anti-proliferative effects. "

Vitamin K1 Foods

Vitamin K1 is said to have a lower absorption rate than vitamin K2, with estimates as low as 10% of the vitamin being absorbed. This could be because K2 foods are often richer in fat, whereas K1 sources are often leafy green vegetables which are low in fat. Hence, eating foods with high amounts of K1 such as kale together with fats like olive oil, coconut oil or avocado could boost absorption significantly.

Fruits don't contain a high amount of K1.

Vegetables High in K1

Kale (cooked) — 443% of the DV per serving
Mustard greens (cooked) — 346% of the DV per serving
Swiss chard (raw) — 332% of the DV per serving
Collard greens (cooked) — 322% of the DV per serving
Spinach (raw) — 121% of the DV per serving
Broccoli (cooked) — 92% of the DV per serving

Vegetables Low in Vitamin K1 , per 1-cup serving, include:

Turnips (raw or cooked) — 0.1 micrograms
Beets (raw or cooked) — 0.3 micrograms
Sweet Corn (raw or cooked) — 0.5 micrograms
Onion (raw or cooked) — 1 microgram per 1 medium onion
Rutabagas (raw or cooked) — 0.5 micrograms
Pumpkin (cooked) — 2 micrograms
Winter squash(cooked) — 2 micrograms
Summer squash (cooked) — 3 micrograms
Eggplants (cooked) — 3 micrograms
Bamboo shoots (raw or canned) — 0 micrograms
Mushrooms (raw or cooked) — 0 micrograms
Tomatoes (cooked) — 7 micrograms
Tomatoes (raw) — 14 micrograms
Carrots — 16.9 mcg
Cucumbers (raw) — 17 micrograms
Iceberg lettuce (raw) — 17.4 micrograms


   
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link to synergies flowchart

link to pathways diagram


   
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Posted by: @j

@rosaleend @laika @chris48 @jens

There's an issue with the formatting so I'm starting this new thread before it gets worse.

Links to previous threads:

TNBC / testing strategies in a NED situation
https://www.cancertreatmentsresearch.com/community/breast-cancer/tnbc-testing-strategies-in-a-ned-situation/

TNBC reoccurrence mets to skin inoperable tumour In right breast and left lymph node involved
https://www.cancertreatmentsresearch.com/community/breast-cancer/tnbc-reoccurrence-mets-to-skin-inoperable-tumour-in-right-breast-and-left-lymph-node-involved/#post-6267

 

Hi Johan - I found the issue and the formatting is good again.

 


   
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@daniel Thanks, D!


   
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Direct inhibition of ACTN4 by ellagic acid limits breast cancer metastasis via regulation of β-catenin stabilization in cancer stem cells

https://jeccr.biomedcentral.com/articles/10.1186/s13046-017-0635-9

(in vivo study in mice, 50m/kg - 55 kg human equivalent dose 222.97 mg)

"EA inhibited breast cancer growth and metastasis via directly targeting ACTN4 in vitro and in vivo, and was accompanied by a limited CSC population. ACTN4 knockdown resulted in the blockage of malignant cell proliferation, colony formation, and ameliorated metastasis potency."

 

Unripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction

"oral administration of RCE showed the potent anti-tumor activity similar to anti-PD-1 antibody. The present study suggests that RCE possesses potent anti-tumor effect via PD-1/PD-L1 blockade, and ellagic acid is the main compound in RCE. Thus, we provide new aspects of RCE as an immunotherapeutic agent."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693366/


   
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to avoid filler there are pomegranate (seed) extracts with 90% ellagic acid, also very inexpensive 


   
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@j I have been looking online....do you happen to know the name of the ellagic acid 90% extract? I see 40% products.  

 

Another question..... what is the difference between HCA (hydroxycitrate) and citrate?  I think you mentioned that CA was for targeting glycolysis and HCA is to target fatty acid synthesis...... so together they interfere with the metabolism of glucose and fatty acids that cancer uses to survive and thrive........ do I have this correct?  I also take atorvastatin.... this should help with the fatty acid synthesis too.... correct?  How much HCA is commonly taken? 

Thanks Johan. 

 


   
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Posted by: @rosed

@j I have been looking online....do you happen to know the name of the ellagic acid 90% extract? I see 40% products.  

 

Another question..... what is the difference between HCA (hydroxycitrate) and citrate?  I think you mentioned that CA was for targeting glycolysis and HCA is to target fatty acid synthesis...... so together they interfere with the metabolism of glucose and fatty acids that cancer uses to survive and thrive........ do I have this correct?  I also take atorvastatin.... this should help with the fatty acid synthesis too.... correct?  How much HCA is commonly taken? 

Thanks Johan. 

 

@rosed Hi Rose, here are a few options for the pomegranate extract (ellagic acid 90%)

https://purebulk.com/products/pomegranate-extract-90-ellagic-acid
Amount Per Serving % Daily Value*
Pomegranate (Punica granatum) Extract (hulls) 500 mg
(Standardized to contain 90% Ellagic Acid)
Other Ingredients: None

https://www.supplemented.co.uk/products/pomegranate-250mg-tablets
Pomegranate Extract 250mg Providing: Ellagic Acid 225mg Pomegranate Extract 10,000mg (40:1) standardised to 250mg, Brown Rice Flour (GF), Bovine Gelatine Capsule Shell

HCA is a derivative of CA but has different anticancer properties,  for example, HCA is an inhibitor of ACLY (a lipogenic enzyme). You have that correct that together they interfere with both processes.

In this study, they used HCA in combination with Orlistat (FAS inhibitor), the human equivalent dose of HCA was 1200mg (55kg). I'll check other studies to look for more information on what dosages could be used. 

Potential additive effects of garcinia cambogia on atorvastatin treated hyperlipidemic patients: randomized crossover clinical study https://www.ijmedicine.com/index.php/ijam/article/view/478

" This study scrutinizes the value of garcinia cambogia in treatment of hyperlipidemia alone or in combination with atorvastatin. It produced significant additive effect with atorvastatin and hence atorvastatine doses can be reduced and substituted with garcinia cambogia for reduction serious atorvastatin associated adverse effects."

Have a great weekend!

 

 

 

 


   
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HCA has also been studied in combination with lipoic acid, at a similar dose (approx 1100mg for 55kg).

In a study using HCA, lipoic acid the addition of octreotide increased the anticancer effect significantly

DOI:10.1007/s10637-011-9692-7

(I'm getting a spam warning reason why I couldn't post the link to the study)


   
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orlistat could also be a good combination with ellagic acid to inhibit PD-1/PDL-1

https://www.semanticscholar.org/paper/Fatty-acid-synthase-inhibitor-orlistat-impairs-cell-Cioccoloni-Aquino/f2b0d6bc552a3b2c8ad3053d659497ff985d926f


   
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Melatonin inhibits triple-negative breast cancer progression through the Lnc049808-FUNDC1 pathway

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285388/

"To further confirm the function of FUNDC1 in vivo, we established mouse xenograft models and found that FUNDC1 knockdown significantly suppressed tumor growth (Fig. ​(Fig.1I)1I) and lung metastasis (Fig. ​(Fig.1J).1J). Our findings demonstrated that FUNDC1 knockdown inhibited TNBC progression."

"Our study confirmed the anticancer effect of melatonin on TNBC cells and found that melatonin inhibited TNBC progression through the lnc049808/miR-101/FUNDC1 axis, a ceRNA regulatory mechanism, which has never been reported."

Melatonin Preserves Blood-Brain Barrier Integrity

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154427

"In conclusion, one of the protective effects of melatonin against BBB hyperpermeability occurs due to enhanced BBB integrity via MMP-9 inhibition."


   
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Successful Treatment by Mistletoe Viscum Album Extract of a Patient with Recurrent Triple Negative Breast Cancer who declined Chemotherapy

https://juniperpublishers.com/jcmah/pdf/JCMAH.MS.ID.555815.pdf


   
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Mistletoe Extract Targets the STAT3-FOXM1 Pathway to Induce Apoptosis and Inhibits Metastasis in Breast Cancer Cells

"our results suggest that mistletoe extract targets the STAT3-FOXM1 pathway for its cytotoxic effects, and that mistletoe extracts might be useful for the treatment of patients with cancers highly expressing the STAT3-FOXM1 pathway."

https://www.worldscientific.com/doi/10.1142/S0192415X21500221


   
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Melatonin abrogates liver, ovarian, and uterine toxicities induced by tamoxifen in a breast cancer mouse model

"melatonin when used in combination with tamoxifen not only helped to reduce the mouse mammary tumour volume but also minimized the toxicities."

https://nopr.niscpr.res.in/bitstream/123456789/55843/1/IJEB%2059(1)%2033-43.pdf


   
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Posted by: @j

Mistletoe Extract Targets the STAT3-FOXM1 Pathway to Induce Apoptosis and Inhibits Metastasis in Breast Cancer Cells

"our results suggest that mistletoe extract targets the STAT3-FOXM1 pathway for its cytotoxic effects, and that mistletoe extracts might be useful for the treatment of patients with cancers highly expressing the STAT3-FOXM1 pathway."

https://www.worldscientific.com/doi/10.1142/S0192415X21500221

 

Identification of FOXM1 as a specific marker for triple‑negative breast cancer
 
Bioinformatics driven discovery of small molecule compounds that modulate the FOXM1 and PPARA pathway activities in breast cancer
 
 

 


   
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Betulinic acid impairs metastasis and reduces immunosuppressive cells in breast cancer models

https://www.oncotarget.com/article/23376/text/

"Anti-metastasis efficacy of BA in subcutaneous 4T1 model. The remarkable inhibitory effects of BA on 4T1 cells metastasis in vitro implied that it might also efficiently inhibit tumor metastasis in vivo. To verify this hypothesis, we investigated the anti-metastasis activity of BA in vivo. Firstly, we used a subcutaneous model using 4T1 cells. Then the tumor-bearing mice were treated daily at the dose of 10 mg/kg for 21 days. There was not different body weight of mice between BA-treated and vehicle-treated groups (Supplementary Figure 4D). However, there was a reduction in tumor growth and tumor weight in the BA-treated groups (Figure 3A, 3B, Supplementary Figure 4A and Supplementary Figure 4C). Moreover, the number of lung metastatic nodules and lungs weight were both decreased after treating by BA (Supplementary Figure 4B, Figure 3C and 3D). In addition, immunohistochemistry analyses were performed to evaluate the anti-metastasis mechanism of BA. As shown in Figure 3E and 3F, BA significantly inhibited the proliferation of nuclear Ki 67 positive cells. Besides, treatment of BA treatment of mice with BA inhibited the expression of MMP-2, MMP-9 and P-Stat3 in 4T1 tumor tissues. Overall, these data suggest that BA could inhibit breast cancer tissues by inhibiting cell proliferation and blocking metastasis,, which is consistent with the results in vitro."

 

Human equivalent dose (55kg) approx 45mg of Betulinic acid. @daniel has a 50mg liposomal BA supplement.


   
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@j Funny, I had seen the Betulinic Acid supplement and was wondering about it!  I have a quick question....what do you think of glutathione?  I saw someone mentioned a supplement called Immunocal?  Just curious on your opinion.  Have a great day.  

 


   
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Posted by: @rosed

@j Funny, I had seen the Betulinic Acid supplement and was wondering about it!  I have a quick question....what do you think of glutathione?  I saw someone mentioned a supplement called Immunocal?  Just curious on your opinion.  Have a great day.  

 

@rosed I'd avoid it! "Our data suggest that NAC and GSH could promote aggressive tumor behavior by reduction of ROS levels." https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-021-00731-0

Have a great day too!

 


   
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Posted by: @j

Posted by: @rosed

@j Funny, I had seen the Betulinic Acid supplement and was wondering about it!  I have a quick question....what do you think of glutathione?  I saw someone mentioned a supplement called Immunocal?  Just curious on your opinion.  Have a great day.  

 

@rosed I'd avoid it! "Our data suggest that NAC and GSH could promote aggressive tumor behavior by reduction of ROS levels." https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-021-00731-0

Have a great day too!

 

from the above mentioned study:

 

* The doses were biologically relevant and were estimated based on the human equivalent dose for
a 60-kg adult, i.e. 600 mg/serving/day for NAC and 500 mg/serving/day for GSH (glutathione)

* After DEN injection, all mice developed multiple foci of HCC at 35 weeks.
Significant body weight loss was observed in the high-dose NAC- and GSH-treated mice
and the latter was accompanied by a decrease in survival rate, while NAC and low-dose
GSH treatments did not affect the survival.

* High-dose GSH treatment significantly enhanced the tumor incidence of the mice

* Significant increases in the tumor masses together with a decrease in intra-tumoral ROS levels
were observed in both low- and high-dose NAC-treated groups. Similarly, with both low- and high-dose
GSH treatments, along with increasing trends in the bioluminescent signals (Fig. 1h), there was a
significant increase in the tumor masses. There was also a significant reduction of ROS levels.

* significantly more metastatic foci were present in the lungs from both the low and high-dose GSH-treated groups when compared with the control group

* NAC and GSH are thiol group (-SH)-containing antioxidants, apart from directly neutralizing ROS, they also provide precursors for endogenous GSH synthesis including cysteine, glutamine and glycine under the regulation of NRF2 (Nuclear Factor, Erythroid 2 like 2), the master gene regulator responding to cellular oxidative stress, and GCLC (Glutamate-cysteine ligase catalytic subunit), and the first rate-limited enzyme in cellular GSH biosynthesis

* GSH treatment at both low and high doses exhibited similar antagonizing effects to Sorafenib-mediated tumor suppression addition of NAC at both low and high doses effectively abrogated such growth suppression (by Sorafenib).

(attachment: GSH content in some foods e.g 1.5mg in 100 grams of apples.  500 mg GSH supplement = GSH content in 33 KG of apples.)

 


   
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@rosed

"the systemic decrease of cysteine levels is proposed as a suitable strategy in cancer clinical management, being supported by pre-clinical studies with promising results in breast and prostate carcinomas and leukemia. "

https://www.frontiersin.org/articles/10.3389/fonc.2020.00947/full


   
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@j I had heard conflicting remarks on it.... so I have avoided it.  Thanks so much!

 


   
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Amalina, N.D., Salsabila, I.A., Zulfin, U.M. et al. In vitro synergistic effect of hesperidin and doxorubicin downregulates epithelial-mesenchymal transition in highly metastatic breast cancer cellsJ Egypt Natl Canc Inst 35, 6 (2023). https://doi.org/10.1186/s43046-023-00166-3

"in this study, we focus on evaluating the anti-metastatic activity of Hsd (hesperidin) to inhibit DOX-induced metastatic on triple negative breast cancer model, 4T1 cells. We found that Hsd, a flavanone glycoside found in citrus fruits, had a cytotoxic effect in a concentration-dependent manner, while in combination with DOX, Hsd significantly enhanced the cytotoxic effect of DOX with the synergism effect of combination treatment [37]. This finding suggested that Hsd may increase cell sensitivity to DOX to promote optimum cytotoxic activity while inhibiting metastatic effect [42, 43]. The increased cytotoxic activity of Hsd in combination with DOX was potentially caused by several factors as Hsd and DOX were simultaneously internalized in the cells, this allowed both compounds to supplement the antitumor effects of the other compounds. In addition, these results provide a general description that Hsd is promising to be developed as a co-chemotherapeutic agent for inhibiting DOX-driven metastatic.

Furthermore, we explored the underlying mechanism of physiological changes due to the Hsd and its combination treatment. We found that in combination treatment, Hsd-DOX significantly promoted an even higher evidence of apoptosis than the Hsd/DOX single treatment. The result of the apoptosis assay showed that Hsd-DOX was giving a synergistic effect. In addition, compared to DOX, a single treatment of Hsd yielded a stronger apoptosis effect. This suggests that the apoptosis effect in combination is predominantly due to the presence of Hsd. A previous study confirmed that Hsd also strongly induces apoptosis on A549 lung and Hela cells [21, 44, 45]. Apoptosis induction is one of the therapeutic strategies for cancer cure that lead to concentrating on the programmed cell death pathway, which is controlled by genes that keep the internal environment stable. The apoptosis rate is an important metric for assessing the therapeutic efficacy of anticancer agents. On the other hand, the combination treatment of Hsd-DOX caused cell to remain in the accumulation in the G0/G1 and G2/M phases. These results indicated that the combination treatment induced cell arrest at G0/G1 and G2/M phases, continued by significant apoptotic cell death in 4T1 cells. Similarly, Hsd and DOX have also been known to cause G0/G1 and G2/M arrest in human lung and breast cancer cells, respectively, by increasing the level of p21 and decreasing the level of cyclin B1 and cyclin D protein in a p53-dependent manner [46, 47]. Considering that, an alteration in cell apoptosis and cell cycle distribution occurred following combination therapy.

During the progression of cancer, certain tumor cells become motile and attack the host tissue, resulting in metastatic disease. Metastasis may arise due to the DOX administration by an increased level of TGF-β and circulating cancer cells on metastatic lung breast cancer cells [48, 49]. In this process, TGF-β activation may drive lamellipodia formation leading to inhibition of wound closure. The formation of lamellipodia requires Rac1 protein and MMP-9 activities, which play a role in tumor invasion [50]. MMP-9 activity is linked to cancer occurrence and progression, DOX promotes MMP-9 activity in human breast cancer cells by regulating the integrin pathway and proteolytic cleavage [51, 52]. In addition, Rac1 expression increases myosin phosphorylation, which cross-links actin filaments and generates contractile force, promoting cell body movement during cell invasion [53, 54]. Active Rac-1 could promote endothelial cell migration by inducing MMP-9 expression.

One of the interesting aspects of Hsd is that it inhibits migration and lamellipodia formation through downregulation of MMP 9 and Rac1 protein [2, 50]. All of the proteins mentioned above are part of signalling networks that have metastatic effects, and Hsd was discovered to interfere with these signalling networks in order to reduce DOX-induced migration. More specifically, in this study, DOX-induced metastatic potential was confirmed by inhibited wound closure rate and induction of lamellipodia formation by upregulation of MMP 9 and Rac1 protein expression after DOX treatment alone without affecting cell viability. Some previous studies revealed that the DOX administration could induce the migration of highly metastatic breast cancer 4T1 cells and MCF7/HER2 + breast cancer cells [15, 55] by activating the TGF-β1 pathway leading to EMT [14]. EMT is the process by which epithelial cells decide to become mesenchymal-like cells, and it is a critical step in the formation of lamellipodia, which leads to cancer metastasis. Afterward, co-treatment with Hsd significantly reversed the inhibition in wound closure and decreased lamellipodia formation by downregulation of MMP-9 and Rac-1 protein expression. The inhibition of cell migration by Hsd might be correlated to a decrease in the level of TGF-β protein leads to NF-κB pathway inactivation, which is an important contributor to block metastasis [56]. As a result, the mechanism by which Hsd inhibits migration in 4T1 cells is most likely due to TGF- and NF-B signalling inhibition; however, this hypothesis requires further investigation.

Metastatic breast cancer cells characterize more by surviving against oxidative conditions and exhibit resistance to chemotherapeutic agents leading to a high incidence of cancer relapse. Several chemotherapeutic agents aggravate this condition through activation of EMT, leading to cancer cell migration. Additional findings of the synergistic effect indicated that a combination of Hsd and DOX is able to elevate the cell death number through apoptosis induction and cell cycle arrest modulation in highly metastatic breast cancer cells. Increased levels of MMP-9 and Rac-1 protein expression under DOX administration caused the lamellipodia formation, causing EMT leading to progressive metastatic. However, the effect of Hsd in lowering cell migration indicates its potential to reduce the side effect of DOX-induced metastatic. Interestingly, in this study, combination therapy of Hsd-DOX significantly inhibits the migratory capacity of DOX through lamellipodia, MMP-9, and Rac-1 protein regulation. These results showed that the anti-metastatic effect of Hsd may be dependent on lamellipodia formation, MMP-9, and Rac-1 protein expression.

Taken together, Hsd inhibited the metastatic ability of DOX-induced highly metastatic breast cancer cells in vitro by lowering MMP-9 and Rac-1 expression, which is closely integrated with cytotoxic activity, apoptosis, and cell cycle regulation. Collectively, these finding denotes the potential of Hsd as a natural co-chemotherapeutic agent to reduce the side effect of DOX-induced migration and prevent cancer recurrence."


   
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In this study in mice, the researchers used a human equivalent dose (55kg) of approx 450mg of hesperidin/day. Bulksupplements dot com sells 100 grams of hesperidin powder with no additives for about us$16.


   
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Another natural substance to prevent metastasis:

Juglone Inhibits Tumor Metastasis by Regulating Stemness Characteristics and the Epithelial-to-Mesenchymal Transition in Cancer Cells both in Vitro and in Vivo

https://www.imrpress.com/journal/FBL/28/2/10.31083/j.fbl2802026/htm

ascorbic acid may enhance the anticancer effect of juglone (black walnut contains juglone)


   
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Metastatic cancer risk reduced by as much as 72% with high-intensity exercise

https://www.cancertreatmentsresearch.com/community/mindbodyspirit/metastatic-cancer-risk-reduced-by-as-much-as-72-with-high-intensity-exercise/#post-6568


   
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Posted by: @j

Metastatic cancer risk reduced by as much as 72% with high-intensity exercise

https://www.cancertreatmentsresearch.com/community/mindbodyspirit/metastatic-cancer-risk-reduced-by-as-much-as-72-with-high-intensity-exercise/#post-6568

the researchers defined high-intensity exercise as exercise where your heart rate is 80-85% of maximum pulse rate e.g. 132 for a 55-year-old.

https://www.dignityhealth.org/articles/how-to-determine-your-maximum-heart-rate

 


   
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Breast cancer cells that preferentially metastasize to lung or bone are more glycolytic, synthesize serine at greater rates, and consume less ATP and NADPH than parent MDA-MB-231 cell

https://pubmed.ncbi.nlm.nih.gov/36805760/


   
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Posted by: @j

Breast cancer cells that preferentially metastasize to lung or bone are more glycolytic, synthesize serine at greater rates, and consume less ATP and NADPH than parent MDA-MB-231 cell

https://pubmed.ncbi.nlm.nih.gov/36805760/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970329/

Cells can obtain serine by either import from the extracellular environment or intracellular synthesis from glucose, and there is increasing evidence that serine biosynthesis from glucose is important for many cancers.

Consistent with serine being a central precursor for biosynthetic metabolism, many tumors depend on the availability of extracellular serine. Xenografts of HCT116 colon cancer cells grow roughly half as fast when mice are fed a serine- and glycine-free diet as opposed to a normal diet (Maddocks et al., 2013).

In human colon cancer and lung cancer cell lines, proliferation in medium that contains serine without glycine is indistinguishable from proliferation in medium containing both amino acids, whereas withdrawal of serine alone affects proliferation to the same degree as depletion of both amino acids (Labuschagne et al., 2014).

Moreover, providing increased concentrations of glycine in the absence of serine results in even more severe suppression of proliferation than withdrawal of both serine and glycine. These findings argue that serine is a vitally important amino acid, and this conclusion is further supported by the observation that cells preferentially take up serine and excrete glycine when serine is available and consume glycine only when serine is depleted. This may explain why glycine depletion strongly correlates with proliferation rate across cancer cells (Jain et al., 2012),

 


   
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