Melatonin Inhibits Warburg-dependent Cancer By Redirecting Glucose Oxidation To The Mitochondria

S.Seneff

Member
Joined
Mar 18, 2020
Messages
172
Melatonin has the ability to intervene in the initiation, progression and metastasis of some experimental cancers. A large variety of potential mechanisms have been advanced to describe the metabolic and molecular events associated with melatonin’s interactions with cancer cells. There is one metabolic perturbation that is common to a large number of solid tumors and accounts for the ability of cancer cells to actively proliferate, avoid apoptosis, and readily metastasize, i.e., they use cytosolic aerobic glycolysis (the Warburg effect) to rapidly generate the necessary ATP required for the high metabolic demands of the cancer cells. There are several drugs, referred to as glycolytic agents, that cause cancer cells to abandon aerobic glycolysis and shift to the more conventional mitochondrial oxidative phosphorylation for ATP synthesis as in normal cells. In doing so, glycolytic agents also inhibit cancer growth. Herein, we hypothesize that melatonin also functions as an inhibitor of cytosolic glycolysis in cancer cells using mechanisms, i.e., downregulation of the enzyme (pyruvate dehydrogenase kinase) that interferes with the conversion of pyruvate to acetyl CoA in the mitochondria, as do other glycolytic drugs. In doing so, melatonin halts the proliferative activity of cancer cells, reduces their metastatic potential and causes them to more readily undergo apoptosis. This hypothesis is discussed in relation to the previously published reports. Whereas melatonin is synthesized in the mitochondria of normal cells, we hypothesize that this synthetic capability is not present in cancer cell mitochondria because of the depressed acetyl CoA; acetyl CoA is necessary for the rate limiting enzyme in melatonin synthesis, arylalkylamine-N-acetyltransferase. Finally, the ability of melatonin to switch glucose oxidation from the cytosol to the mitochondria also explains how tumors that become resistant to conventional chemotherapies are re-sensitized to the same treatment when melatonin is applied.

Reiter, R.J., Sharma, R., Ma, Q. et al. Melatonin inhibits Warburg-dependent cancer by redirecting glucose oxidation to the mitochondria: a mechanistic hypothesis. Cell. Mol. Life Sci. (2020). https://doi.org/10.1007/s00018-019-03438-1
 

lilsticky

Member
Joined
Nov 27, 2019
Messages
79
Whereas melatonin is synthesized in the mitochondria of normal cells, we hypothesize that this synthetic capability is not present in cancer cell mitochondria because of the depressed acetyl CoA;

Hey that's pretty good
 
Similar threads
Thread starter Title Forum Replies Date
Brandin Nicotine effect on melatonin Insomnia, Sleep Issues 18
Highserotonin90 Melatonin Increase PDH Complex Supplements 38
V Melatonin Supplementation Miscellaneous Health Discussions 2
Razvan Melatonin? Insomnia, Sleep Issues 1
HealthisWealth The Manila Doctors Hospital Is The First In The World To Try High-dose Melatonin (36 Mg To 72 Mg/day Supplements, Pharmaceutical Drugs 0
TheBeard Melatonin Reduces Estrogens Through Multiple Pathways Supplements, Pharmaceutical Drugs 17
S.Seneff Evaluation Of The Role Of Melatonin In The Metastasis Of Papillary Thyroid Carcinoma Scientific Studies 1
S.Seneff COVID-19: Melatonin As A Potential Adjuvant Treatment Scientific Studies 4
Mito Melatonin: Master Hormonal Conductor And Scheduler Articles & Scientific Studies 4
T Confused: Melatonin Light 7
N Isn't Estrogen Needed To Make Serotonin To Make Melatonin? Insomnia, Sleep Issues 7
isabella83 Depression, Melatonin, Wifi, Oh My Mental Issues 59
Nicolas Noyola Melatonin And GABA Scientific Studies 2
Captain_Coconut Melatonin, Protects Against LPS / LPO / ROS / RNS Scientific Studies 10
Nicolas Noyola Stimulation Of Melatonin Receptors Decreases Calcium Levels In Xenopus Tectal Cells By Activating GA Scientific Studies 0
DaveFoster Optimal Melatonin Dosage For Insomnia And Delayed Sleep Phase Syndrome (DSPS) Scientific Studies 12
M Help! Melatonin Induced Sexual Dysfunction And More Male Issues 27
M Can I Take Methylene Blue With Melatonin ? Ask For Help or Advice 3
T Revisiting Melatonin Science 9
Mito Melatonin Decreases Glucose Metabolism In Prostate Cancer Cells Articles & Scientific Studies 0
biggirlkisss Lowering Melatonin Levels With Green Light Is There A Point Ask For Help or Advice 0
Drareg Grey Hair And Melatonin Scientific Studies 11
DaveFoster Melatonin - Low-Dose For Sleep Thyroid and Hormones 9
Dan Wich Pranarupa: Magick And Melatonin Blogs 29
DaveFoster Red Light, Melatonin, And Sleep Phase Disorder Insomnia, Sleep Issues 7
Koveras Increased Melatonin Signaling Is A Risk Factor For Type 2 Diabetes Scientific Studies 2
ecstatichamster Melatonin Hinders Sperm Production By LOWERING Estrogen In Men? Scientific Studies 6
David PS Topical Melatonin For Hair Growth And Repigmentation Hair & Nails 5
haidut Melatonin Elevates Brain Serotonin Scientific Studies 21
B Long-term melatonin administration enhances the antioxidant potential of human plasma maintained aft Articles & Scientific Studies 0
S B6 in the Evening Increases Melatonin Articles & Scientific Studies 2
J Melatonin And Confusion Health 29
lovelife Zinc + Melatonin & Acne Zinc 1
P Melatonin Health 10
J Melatonin Ray Peat Quotes 15
N Melatonin: Noooooooooooooooooo! Supplements 10
cjm "Vitamin E inhibits the activation of NF‐kB, with the greatest inhibition seen with the succinate form." Scientific Studies 2
H Apigenin inhibits rat neurosteroidogenic 5α-reductase 1 and 3α-hydroxysteroid dehydrogenase Scientific Studies 2
O Doxycycline Inhibits Cancer Stem Cell-Like Properties via PAR1/FAK/PI3K/AKT Pathway in Pancreatic Cancer Scientific Studies 2
A Octreotide Inhibits GH, Serotonin, Prolactin, TSH, Insulin Supplements, Pharmaceutical Drugs 0
Mito Methylene Blue Inhibits the SARS-CoV-2 Spike-ACE2 Protein Miscellaneous Health Discussions 6
shine PQQ inhibits lactate formation, increases lactate to pyruvate conversion, improves NAD+/NADH ratio Scientific Studies 0
haidut Androgens Boost, Estrogen Inhibits, Anti-aging Gene Klotho Scientific Studies 1
haidut Estrogen Lowers T, DHT, And Fertility; Inhibits 5α-Reductase (5-AR) Scientific Studies 13
meatbag Cod-liver Oil Inhibits Gastric Secretion Articles & Scientific Studies 7
Hgreen56 Niacinamide Inhibits Fatloss And Niacin Improve It? Supplements, Pharmaceutical Drugs 10
S.Seneff Russia Compounds That Chelate Iron And Inhibits Potential Mitochlndrial Calcium Overload Scientific Studies 1
haidut High-salt Diet Strongly Inhibits Cancer Growth Scientific Studies 12
S COVID-19 Aspirin Inhibits Antibody Production In Human Cells Viruses, Parasites, Fungus, Vaccines 15
GorillaHead Quercetin Inhibits Finasteride From Reducing Serum DHT? Scientific Studies 10

Similar threads

Top