HER2+ breast cancer cells undergo apoptosis upon exposure to tannic acid released from remodeled cross-linked collagen type I
Tannic acid (TA) is a naturally occurring polyphenol that cross-links collagen type I and possesses anticancer potential. In previous studies, we demonstrated the increased sensitivity of estrogen receptor-positive (ER+ ) breast cancer cells to TA as opposed to triple negative breast cancer cells and normal human breast epithelial cells. In the current study, human pre-adipocytes and HER2+ breast cancer cells were grown on TA cross-linked collagen type I beads. Cell attachment, growth, and proliferation of the cells result in remodeling of the collagen matrix and release of the cross-linking TA. TA concentrations in the conditioned media were determined. Induced apoptosis of cells grown on the TA cross-linked collagen type I beads was imaged and quantified. Viability of HER2+ breast cancer cells and normal breast epithelial cells after exposure TA released from bead remodeling was quantified. Caspase gene expression and protein expression were evaluated. HER2+ breast cancer cells underwent caspase-mediated apoptosis in response to TA exposure. TA-induced apoptosis in a concentration- and time-dependent manner, with HER2+ breast cancer cells demonstrating an increased sensitivity to the TA effects.
https://www.amazon.com/Tannic-Powder-Crystals-Reagent-Purity/dp/B083L937G1
edit: the product link shouldn't have been included (I copy/paste too fast 😉
Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF- κ B signaling (TNBC)
Our results confirmed that matrine significantly suppressed the proliferation of highly-metastatic human breast cancer MDA-MB-231 cell line. Matrine displayed synergistic effects with existing anticancer agents celecoxib,...
Matrine is available from Liftmode
"Treatment of MCF7, BT-474 and MDA-MB-231 cells with matrine decreased the expression of IKKβ by ≤95%, according to the calculated OD values of the IKKβ bands relative to the cellular protein β-actin bands. These results indicated that matrine significantly decreased IKKβ expression in the treated breast cancer cells, suggesting that matrine effectively inhibited the proliferation of breast cancer cells by a mechanism associated with IKKβ"
https://pubmed.ncbi.nlm.nih.gov/24137358/
BT-474 (HER2+ cell line)
https://egrove.olemiss.edu/cgi/viewcontent.cgi?article=2357&context=hon_thesis
The Effects of Alpha-Tocopherol and Ascorbic Acid on Metastatic
Breast Cancer Cells
Interesting results, and again show that vitamin E can stimulate tumor proliferation.
Vitamin C proved somewhat effective in an MCF-7 cell line, much less in TNBC.
Highly Metastatic Subpopulation of TNBC Cells Has Limited Iron Metabolism and Is a Target of Iron Chelators
https://pubmed.ncbi.nlm.nih.gov/36672419/
Btw, citric acid is an iron chelator
Highly Metastatic Subpopulation of TNBC Cells Has Limited Iron Metabolism and Is a Target of Iron Chelators
https://pubmed.ncbi.nlm.nih.gov/36672419/
Btw, citric acid is an iron chelator
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
Both naringin and citric acid also decrease ammonia!
High plasma vitamin B-6 and riboflavin may lower breast cancer risk, especially in premenopausal women. Additional research is necessary to further explore these associations.
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
(see attached image)
Life Extension Circadian Sleep has 50mg nobiletin with 1,5 melatonin per capsule. US$21 30 caps.
Fluvastatin synergistic with Honokiol
This is very interesting! Do you think it is also synergistic with other statins? Part of Bianca's protocol is Atorvastatin, therefore I am wondering whether it makes sense to add it.
Any opinions on whole-body cryotherapy????
Seki, T., Yang, Y., Sun, X. et al. Brown-fat-mediated tumour suppression by cold-altered global metabolism. Nature 608, 421–428 (2022). https://doi.org/10.1038/s41586-022-05030-3
This is interesting! I am following the Wim Hof Method and I am taking cold showers and ice baths for years. The method also contains a breathing technique that alters the immune function. Especially the breath work seems to significantly increase blood ph for several hours ( https://www.pnas.org/doi/10.1073/pnas.1322174111 ). This and other studies also show that it has strong anti-inflammatory effects (e.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886760/ ) and improves (or at least changes) the immune function.
Here you can also find an intersting discussion about the possible effects on cancer: https://medicalsciences.stackexchange.com/questions/13926/is-a-hyperventilationhypoventilation-breathing-exercise- wim-hof-method-more-l
In regard to cancer I was very sceptical about the value of the ice baths, because I thought it makes more sense to go the other way with hypothermia. Anyway, the breathwork always seemed promising to me. I thought it might help when following an alcalinization strategy.
They also have a seperate facebook group for cancer: https://www.facebook.com/groups/wimhofmethodcancersurvivorsandsupport
I started the WHM because my whole life I got sick 2-4 times per year, often coughing and sneezing for several weeks. After starting this method I have not been sick at all for 5 years now. Plus, I am never really cold anymore. Before I was always wearing several layers during winter and was still always freezing.
Bianca did the breathing technique a couple of times during her carboplatin+nab-paclitaxel chemo when her leucocytes were down, because based on the studies it should increase those. Anyway, it was hard to tell if it helped.
Fluvastatin synergistic with Honokiol
This is very interesting! Do you think it is also synergistic with other statins? Part of Bianca's protocol is Atorvastatin, therefore I am wondering whether it makes sense to add it.
I'd bet it is, Chris. And combining statins is not a problem https://pubmed.ncbi.nlm.nih.gov/21107758/
In the event of TNBC recurrence, it seems there's a high probability that there are changes to the types of cancer cells, "8 out of 13 initially triple-negative patients (61.5%) had a change to positive status of either ER, PR, or HER2".{ref} I've posted an article in this or the other TNBC thread making the case for the use of Tamoxifen in TNBC. In my view, in a recurrence and in light of this data, it makes even more sense to try Tamoxifen and especially in combination with substances that might enhance its effectiveness. It's an old drug, there's just not much interest in it anymore as it's not a profitable drug. I've attached a diagram with some additional options for Her2+.
for updates please check https://synergiesforcancertreatments.blogspot.com/p/triple-negative-breast-cancer-tnbc.html
@j Thank you for these amazing diagrams. I am adding this new Her2 diagram to my war room strategy wall 😉. It really is like a war. So my enemy is deciding to employ some new receptors and locations..... but I am lucky to have someone throwing some new weaponry suggestions my way. Awesome. I am looking at magnolol and Acetazolamide right now! I was also looking at Ursolic Acid and just realized that I am taking it in the MCS "Glutamine Inhibifour"..... funny I was going to look up the contents of that today because it blocks glutamine.... and there it was..... Ursolic Acid. Now I need to make sure I am taking enough. Getting some further bloodwork and analysis of tumor. So far.... 75% Her2 and rest TNBC. Looking at PDL-1 status. Maybe that increased too..... will be interesting. Feel like I am getting recognizance on the enemy!!!!!! Thanks for all the input, Johan. I took a cancer break yesterday..... back on the case today.
@j Thank you for these amazing diagrams. I am adding this new Her2 diagram to my war room strategy wall 😉. It really is like a war. So my enemy is deciding to employ some new receptors and locations..... but I am lucky to have someone throwing some new weaponry suggestions my way. Awesome. I am looking at magnolol and Acetazolamide right now! I was also looking at Ursolic Acid and just realized that I am taking it in the MCS "Glutamine Inhibifour"..... funny I was going to look up the contents of that today because it blocks glutamine.... and there it was..... Ursolic Acid. Now I need to make sure I am taking enough. Getting some further bloodwork and analysis of tumor. So far.... 75% Her2 and rest TNBC. Looking at PDL-1 status. Maybe that increased too..... will be interesting. Feel like I am getting recognizance on the enemy!!!!!! Thanks for all the input, Johan. I took a cancer break yesterday..... back on the case today.
About ursolic acid, there's 100mg in that formula, a good dose. In studies a wide range of dosages has been used and regarding bioavailability "Collectively, the limited animal studies indicate that oral administration of UA can
result in plasma UA levels in the nano-to-micromolar range, at concentrations close to those used in the majority of the in vitro studies showing potent anticancer effects. " https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9655894/
IHERB has a 200mg option with quite a bit of filler, supersmart a 300mg option Ursolic acid (from 1200 mg of rosemary leaves standardized to 25% ursolic acid) 300 mg Other ingredients: Acacia gum, rice flour.
Here's a very interesting study:
Drivers and suppressors of triple-negative breast cancer
https://www.pnas.org/doi/10.1073/pnas.2104162118
In the study they say that "Triple-negative breast cancer (TNBC) is not estrogen or progesterone dependent but several laboratories have reported the presence of estrogen receptor β (ERβ) in 20 to 30% of TNBCs (1–6). Lobular cancer also expresses ERβ (7), and these observations have led to the suggestion that ERβ could be targeted in treatment of these cancers. Most studies to date have found that ERβ represses proliferation and migration in cancers (2, 8–12) but there are also studies showing that ERβ induces a more aggressive phenotype in TNBC cells (4, 13)."
In addition, they say that "The high expression of these two MMPs in TNBC suggests an absence of ERβ-suppressive function and may indicate an ERα-like action (activation at EREs) of ERβ."
"In the present study, the limited effect of ERβ expression in TNBC suggests caution in extrapolation from TNBC cell lines to human TNBC samples. The MDA-MB-231 cell line was isolated from a patient with invasive ductal carcinoma (IDC) which expressed ERα (48). All of the other TNBC cell lines were also derived from breast cancers that were not originally TNBC (49). These cell lines do have in common with TNBC the lack of expression of ER, PR, or HER2 but that does not make them true representatives of TNBC. This difference between the TNBC cell lines and TNBC in patient samples may explain why other pathways previously reported to be involved in TNBC cell lines (GPNMP, EGFR, Notch 1–3, mTOR, AKT 1 and 2, TGFβ, activin receptor, SMAD 7) were all down-regulated in RNA-seq of the TNBC patient samples."
This study suggests that caution when using ERβ agonists is needed.
(via Wikipedia) Agonists of ERβ selective over ERα include:
- 20-Hydroxyecdysone(ecdysterone, 20-HE, 20-E) —phytoecdysteroid[37]
- 3β-Androstanediol(3β-diol) –endogenous
- 8β-VE2
- AC-186
- Apigenin–phytoestrogen[38]
- Daidzein– phytoestrogen[38]
- DCW234
- Dehydroepiandrosterone(DHEA) – endogenous
- Diarylpropionitrile(DPN)
- ERB-79and its active enantiomerERB-26
- ERB-196(WAY-202196)
- Erteberel(SERBA-1, LY-500307)
- FERb 033– 62-fold selectivity for ERβ over ERα[39]
- Genistein– phytoestrogen; 16-fold selectivity for ERβ over ERα[38]
- Liquiritigenin(Menerba) – phytoestrogen[38]
- Penduletin– phytoestrogen[38]
- Prinaberel(ERB-041, WAY-202041)
- S-Equol((S)-4',7-isoflavandiol) – phytoestrogen; 13-fold selectivity for ERβ over ERα[38]
- WAY-166818
- WAY-200070
- WAY-214156
Genistein but also Apigenin are listed as Agonists of ERβ.
Tamoxifen is an antagonist.
" There were two unexpected findings: 1) a strong induction of CYPs involved in activation of fatty acids (CYP4), and in inactivation of calcitriol (CYP24A1) and retinoic acid (CYP26A1); and 2) a marked down-regulation of FOS, FRA1, and JUN, known tethering partners of ERβ. ERβ is expressed in 20 to 30% of TNBCs and is being evaluated as a target for treating TNBC. We used ERβ+ TNBC patient-derived xenografts in mice and found that the ERβ agonist LY500703 had no effect on growth or proliferation. Expression of CYPs was confirmed by immunohistochemistry in formalin-fixed and paraffin-embedded (FFPE) TNBC. In TNBC cell lines, the CYP4Z1-catalyzed fatty acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) increased proliferation, while calcitriol decreased proliferation but only after inhibition of CYP24A1. We conclude that CYP-mediated pathways can be drivers of TNBC but that ERβ is unlikely to be a tumor suppressor because the absence of its main tethering partners renders ERβ functionless on genes involved in proliferation and inflammation."
also, see attachment, calcitriol (the activated form of vitamin D3) and ketoconazole show strong inhibition
another finding of that study "Genes involved in the regulation of pH were very highly expressed in TNBC. Maintenance of an acidic environment of cancer is a well-characterized phenomenon which gives cancer cells a growth advantage over normal cells (52)."
note that apigenin is a weak Erβ agonist, genistein much stronger.
@medline what do you think of the use of apigenin in TNBC?
@chris48 Cancer treatment is so miserable ..... hard to even think of ice cold showers/baths 😬 .... that's why the notion of a 3 minute chamber sounded more manageable to me. I can't say it sounds all that much more appealing though. I will continue to investigate..... I will let you know if I decide to try. My immune system is still low from all my ACT/Carbo chemo and now they want to dump more in to me. Plenty of decisions upcoming. All my best to Bianca.
