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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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| CLOCK (Circadian Locomotor Output Cycles Kaput) is a core circadian-rhythm transcription factor with major roles in cell-cycle control, metabolism, DNA repair, and immune function — all of which influence cancer. Increasing evidence shows that circadian disruption and altered CLOCK activity can drive tumorigenesis, progression, and therapy resistance. In many cancers, CLOCK is overexpressed or constitutively active, leading to: -↑ cell proliferation -↑ resistance to apoptosis -↑ survival pathways -↑ stemness Cancer stemness often correlates with: ↑ CLOCK expression Tumor Types Where CLOCK Is Often Upregulated: Breast, Colorectal, HCC, GBM, NSCLC, Ovarian, Prostate, Pancreatic cancer Overexpression often correlates with: -higher grade -poor differentiation -worse survival Natural Products that may modulate CLOCK: -Melatonin -Resveratrol -Curcumin -EGCG -Quercetin -Berberine -Vitamin D3 -Sulforaphane -EPA/DHA -Silymarin/Silibinin -Honokiol Indirect Modulation of CLOCK: -Butyrate (SCFA) – HDAC inhibitor; boosts PER/Cry cycling -Genistein (soy isoflavone) – alters CLOCK and BMAL1 methylation -Apigenin – affects BMAL1 and PER2; suppresses cancer growth -Luteolin – modulates CLOCK through NF-κB/IL-6 pathways Circadian disruption in cancer and regulation of cancer stem cells by circadian clock genes: An updated review Potential Role of the Circadian Clock in the Regulation of Cancer Stem Cells and Cancer Therapy Can we utilise the circadian clock to target cancer stem cells? |
| 4705- | MEL, | Melatonin: beyond circadian regulation - exploring its diverse physiological roles and therapeutic potential |
| - | Review, | Nor, | NA |
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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