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| Hormone in the body made by pineal gland. • Melatonin is a potent antioxidant. It neutralizes reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are involved in DNA damage and cancer progression. • Melatonin has been shown to modulate apoptotic pathways by influencing mitochondrial permeability, cytochrome c release, and caspase activation. • In several cancer cell models, melatonin appears to promote apoptosis in malignant cells while sparing normal cells. The most well-known indolamines are serotonin and melatonin, both of which play significant roles in regulating mood, sleep, and overall mental well-being. Melatonin doses (20 mg to even 40 mg per day), often given as an adjuvant treatment for cancer. -The plasma half-life of melatonin is generally in the range of approximately 20 to 60 minutes -It has been suggested that administering melatonin at the appropriate phase of the circadian cycle may enhance its anti-tumor activity and reduce the side effects of chemotherapy and radiation therapy. Bio-availability: Oral melatonin has a low and variable bio-availability (often estimated between 3% and 33%), which means that only a fraction of the ingested dose reaches the bloodstream unchanged. For proOxidant effect might need >10uM, which might be 100mg dose (assuming 10% bio-availability) Might also be required X10 levels? -It remains unknown whether the pro-oxidant action exists in vivo. the vast majority of evidence indicates that melatonin is a potent antioxidant in vivo even at pharmacological concentrations. Interactions: -Melatonin could potentially add to the blood pressure–lowering properties of antihypertensive drugs. -Patients using insulin should be monitored for changes in blood glucose levels. -Melatonin might interact with drugs like warfarin, aspirin, or clopidogrel.(antiplatelet) Melatonin Cancer Relevant Pathways
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| Hypoxia-Inducible-Factor 1A (HIF1A gene, HIF1α, HIF-1α protein product) -Dominantly expressed under hypoxia(low oxygen levels) in solid tumor cells -HIF1A induces the expression of vascular endothelial growth factor (VEGF) -High HIF-1α expression is associated with Poor prognosis -Low HIF-1α expression is associated with Better prognosis -Functionally, HIF-1α is reported to regulate glycolysis, whilst HIF-2α regulates genes associated with lipoprotein metabolism. -Cancer cells produce HIF in response to hypoxia in order to generate more VEGF that promote angiogenesis Key mediators of aerobic glycolysis regulated by HIF-1α. -GLUT-1 → regulation of the flux of glucose into cells. -HK2 → catalysis of the first step of glucose metabolism. -PKM2 → regulation of rate-limiting step of glycolysis. -Phosphorylation of PDH complex by PDK → blockage of OXPHOS and promotion of aerobic glycolysis. -LDH (LDHA): Rapid ATP production, conversion of pyruvate to lactate; HIF-1α Inhibitors: -Curcumin: disruption of signaling pathways that stabilize HIF-1α (ie downregulate). -Resveratrol: downregulate HIF-1α protein accumulation under hypoxic conditions. -EGCG: modulation of upstream signaling pathways, leading to decreased HIF-1α activity. -Emodin: reduce HIF-1α expression. (under hypoxia). -Apigenin: inhibit HIF-1α accumulation. |
| 1782- | MEL, | Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities |
| - | Review, | Var, | NA |
| 971- | MEL, | Melatonin down-regulates HIF-1 alpha expression through inhibition of protein translation in prostate cancer cells |
| - | in-vitro, | Pca, | DU145 | - | in-vitro, | Pca, | PC3 | - | in-vitro, | Pca, | LNCaP |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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