Notifications
Clear all

Cool room temperature inhibited cancer growth in mice

12 Posts
2 Users
12 Likes
215 Views
medline
(@aliml2)
Joined: 8 months ago
Posts: 124
Topic starter  

Turning down the thermostat seems to make it harder for cancer cells to grow, according to a study in mice by researchers at Karolinska Institutet in Sweden. The study, published in the journal Nature, found that chilly temperatures activate heat-producing brown fat that consumes the sugars the tumors need to thrive. Similar metabolic mechanisms were found in a cancer patient exposed to a lowered room temperature.


   
johan and johan reacted
Quote
medline
(@aliml2)
Joined: 8 months ago
Posts: 124
Topic starter  

In cold rooms, the activity of the fight-or-flight system (sympathetic) decreases and the rest-and-digest system (parasympathetic) increases, which is mediated by the vagus nerve. Sleeping on your right side, chewing gum, coffee enemas, fasting, belly breathing, eating fiber, seafood, etc. also stimulate the vagus nerve and parasympathetic nervous system.

19 Factors That May Stimulate Your Vagus Nerve Naturally

https://health.selfdecode.com/blog/32-ways-to-stimulate-your-vagus-nerve-and-all-you-need-to-know-about-it

If you have an active vagus nerve, cancer stage may no longer be important!

https://pubmed.ncbi.nlm.nih.gov/25001652


   
ReplyQuote
medline
(@aliml2)
Joined: 8 months ago
Posts: 124
Topic starter  

Compounds with activating effect to UCP1 expression identified in the screening.

Drug, Name: Tazarotene, Acitretin, Artemether, Tretinoin, Isotretinoin, Pioglitazone, HCI, Sutent, Li-Adrenaline, Clofazimine, Artemisinin, Adapalene, Epinephrine, Bitartratc, Rifapentine, Indacaterol, Maleate, Formoterol, Hemifumarate, Noradrenaline, Bitartrate, Monohydrate, Indomethacin, Bexarotene, Ethacridine, Lactate, Monohydrate, Rosiglitazonc, I, ICI, Lonidamine, Zafirlukast, Nitrofural, Ketoprofen, Meloxicam, Metaproterenol, Sulfate, Acetylcysteine, Erdosteine, Pitavastatin, Calcium, Teniposide, Dasatinib, Telaprevir, Fenoprofen, Calcium, Hydrate, Candesartan, Cilexetil, Doxazosin, Mesylate, Pizotifen, Malate, Ractopamine, HCI, Tianeptine, Sodium, Methotrexate, Temsirolimus, Isoetharine, Mesylate, Resveratrol

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286640/


   
ReplyQuote
johan
(@j)
Joined: 4 years ago
Posts: 1191
 

VERY interesting! Knowing there are approaches to inhibit cancer growth day AND night makes a huge difference. Great stuff!


   
medline and medline reacted
ReplyQuote
johan
(@j)
Joined: 4 years ago
Posts: 1191
 
Posted by: @aliml2

Compounds with activating effect to UCP1 expression identified in the screening.

Drug, Name: Tazarotene, Acitretin, Artemether, Tretinoin, Isotretinoin, Pioglitazone, HCI, Sutent, Li-Adrenaline, Clofazimine, Artemisinin, Adapalene, Epinephrine, Bitartratc, Rifapentine, Indacaterol, Maleate, Formoterol, Hemifumarate, Noradrenaline, Bitartrate, Monohydrate, Indomethacin, Bexarotene, Ethacridine, Lactate, Monohydrate, Rosiglitazonc, I, ICI, Lonidamine, Zafirlukast, Nitrofural, Ketoprofen, Meloxicam, Metaproterenol, Sulfate, Acetylcysteine, Erdosteine, Pitavastatin, Calcium, Teniposide, Dasatinib, Telaprevir, Fenoprofen, Calcium, Hydrate, Candesartan, Cilexetil, Doxazosin, Mesylate, Pizotifen, Malate, Ractopamine, HCI, Tianeptine, Sodium, Methotrexate, Temsirolimus, Isoetharine, Mesylate, Resveratrol

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286640/

Artemisinin keeps popping up, I have no doubt that it's a very useful broad-spectrum anticancer substance.


   
medline and medline reacted
ReplyQuote
johan
(@j)
Joined: 4 years ago
Posts: 1191
 

I might as well steer folks in the right direction 🙂 Here's a great Artemisinin product, by MCSformulas:

https://www.mcsformulas.com/en/vitamins-supplements/artemisinin-artemisia-annua/


   
medline and medline reacted
ReplyQuote
medline
(@aliml2)
Joined: 8 months ago
Posts: 124
Topic starter  
Posted by: @j

I might as well steer folks in the right direction 🙂 Here's a great Artemisinin product, by MCSformulas:

https://www.mcsformulas.com/en/vitamins-supplements/artemisinin-artemisia-annua/

I have never used Artemisinin, does it cause a feeling of heat in the body? Because UCP1 activators produce heat!


   
ReplyQuote
medline
(@aliml2)
Joined: 8 months ago
Posts: 124
Topic starter  
Posted by: @aliml2

Compounds with activating effect to UCP1 expression identified in the screening.

Drug, Name: Tazarotene, Acitretin, Artemether, Tretinoin, Isotretinoin, Pioglitazone, HCI, Sutent, Li-Adrenaline, Clofazimine, Artemisinin, Adapalene, Epinephrine, Bitartratc, Rifapentine, Indacaterol, Maleate, Formoterol, Hemifumarate, Noradrenaline, Bitartrate, Monohydrate, Indomethacin, Bexarotene, Ethacridine, Lactate, Monohydrate, Rosiglitazonc, I, ICI, Lonidamine, Zafirlukast, Nitrofural, Ketoprofen, Meloxicam, Metaproterenol, Sulfate, Acetylcysteine, Erdosteine, Pitavastatin, Calcium, Teniposide, Dasatinib, Telaprevir, Fenoprofen, Calcium, Hydrate, Candesartan, Cilexetil, Doxazosin, Mesylate, Pizotifen, Malate, Ractopamine, HCI, Tianeptine, Sodium, Methotrexate, Temsirolimus, Isoetharine, Mesylate, Resveratrol

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286640/

Since it is not possible to edit the posts, I reposted the correct list!

Tazarotene
Acitretin
Artemether
Tretinoin
Isotretinoin
Pioglitazone HCI
Sutent
Li-Adrenaline
Clofazimine
Artemisinin
Adapalene
Epinephrine Bitartrate
Rifapentine
Indacaterol Maleate
Formoterol Hemifumarate
Noradrenaline Bitartrate Monohydrate
Indomethacin
Bexarotene
Ethacridine Lactate Monohydrate
Rosiglitazonc HCI
Lonidamine
Zafirlukast
Nitrofural
Ketoprofen
Meloxicam
Metaproterenol Sulfate
Acetylcysteine
Erdosteine
Pitavastatin Calcium
Teniposide
Dasatinib
Telaprevir
Fenoprofen Calcium Hydrate
Candesartan Cilexetil
Doxazosin Mesylate
Pizotifen Malate
Ractopamine HCI
Tianeptine Sodium
Methotrexate
Temsirolimus
Isoetharine Mesylate
Resveratrol


   
ReplyQuote
medline
(@aliml2)
Joined: 8 months ago
Posts: 124
Topic starter  

Targeted mitochondrial uncoupling beyond UCP1 - The fine line between death and metabolic health

In the early 1930s, the chemical uncoupling agent 2,4-dinitrophenol (DNP) was promoted for the very first time as a powerful and effective weight loss pill but quickly withdrawn from the market due to its lack of tissue-selectivity with resulting dangerous side effects, including hyperthermia and death. Today, novel mitochondria- or tissue-targeted chemical uncouplers with higher safety and therapeutic values are under investigation in order to tackle obesity, diabetes and fatty liver disease. Moreover, in the past 20 years, transgenic mouse models were generated to understand the molecular and metabolic consequences of targeted uncoupling, expressing functional uncoupling protein 1 (UCP1) ectopically in white adipose tissue or skeletal muscle. Similar to the action of chemical mitochondrial uncouplers, UCP1 protein dissipates the proton gradient across the inner mitochondrial membrane, thus allowing maximum activity of the respiratory chain and compensatory increase in oxygen consumption, uncoupled from ATP synthesis. Consequently, targeted mitochondrial uncoupling in adipose tissue and skeletal muscle of UCP1-transgenic mice increased substrate metabolism and ameliorates obesity, hypertriglyceridemia and insulin resistance. Further, muscle-specific decrease in mitochondrial efficiency promotes a cell-autonomous and cell-non-autonomous adaptive metabolic remodeling with increased oxidative stress tolerance. This review provides an overview of novel chemical uncouplers as well as the metabolic consequences and adaptive processes of targeted mitochondrial uncoupling on metabolic health and survival.

https://pubmed.ncbi.nlm.nih.gov/27916644/

DNP is probably the most potent activator of UCP1.

https://en.wikipedia.org/wiki/2,4-Dinitrophenol


   
ReplyQuote
medline
(@aliml2)
Joined: 8 months ago
Posts: 124
Topic starter  

Antihelminthic drug for T2DM therapy?

Niclosamide, a drug used to treat intestinal tapeworm infections, has potential as a new antidiabetic therapy, suggest findings published in Nature Medicine. Niclosamide ethanolamine, a salt form of niclosamide, improved features of type 2 diabetes mellitus (T2DM) in mice by inducing mitochondrial uncoupling.

“Developing drugs for reducing hepatic or muscular accumulation of lipids is the way to go for treating T2DM,” says Shengkan Jin, senior author of the study. “The challenge is to find a safe and practical approach to do so.”

Jin's group had previously generated a mouse model in which autophagy is defective in adipose tissue. These mice are lean and do not develop insulin resistance when consuming a high-fat diet (HFD). Mitochondria accumulate and are uncoupled in the adipose tissue of the mice. “This amazing phenotype prompted us to seek pharmacological approaches to achieve the same effect,” Jin explains.

Drugs that induce mitochondrial uncoupling, such as 2,4-dinitrophenol (DNP), have previously been used in humans, but adverse effects at high doses have prevented their establishment as safe antidiabetic therapies. In 2013, a liver-targeted derivative of DNP with a higher therapeutic index than DNP was shown to reduce accumulation of fat in the liver and improve insulin resistance in rats.

Niclosamide acts by uncoupling the mitochondria of parasitic worms. Niclosamide ethanolamine has a good safety profile and is more bioavailable than niclosamide. The researchers observed that C57BL/J mice consuming a HFD that were treated with niclosamide ethanolamine had increased energy expenditure and improved metabolism. Mice with HFD-induced T2DM that were treated with niclosamide ethanolamine had lower fasting blood glucose and basal plasma insulin levels, were more insulin-sensitive and had less hepatic steatosis than diabetic mice that did not receive the drug. Glycaemic control was also improved in db/db mice receiving niclosamide ethanolamine.

Jin comments that the study findings are consistent with the previous reports on the effects of DNP. “The outcome is also consistent with data documenting that transgenic mice with ectopic expression of UCP1 (uncoupling protein 1) in liver, muscle or white adipose tissue exhibit exactly the same phenotypes as our mice treated with niclosamide ethanolamine.”

The potential to use niclosamide ethanolamine and related compounds to treat T2DM in humans is now going to be investigated in preclinical studies required by the FDA, says Jin. The researchers are also synthesizing and testing new compounds with better efficacy and safety profiles than niclosamide ethanolamine.

References

  1. Tao, H. et al. Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice. Nat. Med. 10.1038/nm.3699

https://www.nature.com/articles/nrendo.2014.183

Nicosamide, like acetyl salicylic acid (aspirin), salicylic acid, salicylamide, sodium salicylate and diflunisal, is a derivative of salicylic acid.

https://pubmed.ncbi.nlm.nih.gov/8830801/

I don't know if it's a coincidence or not, but aspirin warms me up!

 


   
johan and johan reacted
ReplyQuote
johan
(@j)
Joined: 4 years ago
Posts: 1191
 
Posted by: @aliml2
Posted by: @j

I might as well steer folks in the right direction 🙂 Here's a great Artemisinin product, by MCSformulas:

https://www.mcsformulas.com/en/vitamins-supplements/artemisinin-artemisia-annua/

I have never used Artemisinin, does it cause a feeling of heat in the body? Because UCP1 activators produce heat!

Good question. I have used many supplements but haven't tried ART yet. Next one on the list!


   
medline and medline reacted
ReplyQuote
medline
(@aliml2)
Joined: 8 months ago
Posts: 124
Topic starter  
Posted by: @aliml2

DNP is probably the most potent activator of UCP1.

https://en.wikipedia.org/wiki/2,4-Dinitrophenol

2,4-dinitrophenol as an anti-cancer drug

2,4-dinitrophenol (DNP) is a lipophilic anionic (-1) protonophore. It can cross membranes protonated, then lose the proton and return as the anion, then reprotonate and repeat the cycle. It was legally (1933–38, USA), and is now illegally, used as dieting drug. It can be bought over the internet and does cause weight loss [138]. However, the therapeutic margin between a slimming and poisonous dose, which can cause death by overheating [139], is close (3–10 fold) [136]. There were reports of cataracts as a side effect in the 1930s but this relation has been later queried [140]. In the correct doses, the deleterious effects of DNP are few [141]. It has been taken by hundreds of thousands of people, often without proper medical consultation, and typically without ill effect [141]. From 1900–2011 (>100 years), there were 62 deaths in the medical literature attributed to DNP [139]; but some of these were intentional, suicide acts. Although not appropriate as a weight loss pharmaceutical, DNP may be useful as a cancer drug. The risk-reward axis is different for terminal patients – with just days, weeks or months to live – than for healthy adults chasing aesthetic goals. Moreover, a further distinction is that the cancer, with its hyperpolarised ΨIM, will accumulate and sequester the drug from normal cells. Incidentally, low doses of DNP increase lifespan in healthy mice [142].


   
ReplyQuote
Share: