Description: <b>Hormone</b> in the body made by pineal gland.<br>
• 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.<br>
• Melatonin has been shown to modulate apoptotic pathways by influencing mitochondrial permeability, cytochrome c release, and caspase activation.<br>
• In several cancer cell models, melatonin appears to promote apoptosis in malignant cells while sparing normal cells.<br>
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The most well-known indolamines are serotonin and melatonin, both of which play significant roles in regulating mood, sleep, and overall mental well-being.<br>
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Melatonin doses (20 mg to even 40 mg per day), often given as an adjuvant treatment for cancer.<br>
-The plasma half-life of melatonin is generally in the range of approximately 20 to 60 minutes<br>
-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.<br>
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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.<br>
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For proOxidant effect might need >10uM, which might be 100mg dose (assuming 10% bio-availability) Might also be required X10 levels?<br>
-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.<br>
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Interactions:<br>
-Melatonin could potentially add to the blood pressure–lowering properties of antihypertensive drugs.<br>
-Patients using insulin should be monitored for changes in blood glucose levels.<br>
-Melatonin might interact with drugs like warfarin, aspirin, or clopidogrel.(antiplatelet)<br>
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Melatonin Cancer Relevant Pathways
<table border="1" cellspacing="0" cellpadding="4">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells</th>
<th>Normal Cells</th>
<th>Label</th>
<th>Primary Interpretation</th>
<th>Notes</th>
</tr>
<tr>
<td>1</td>
<td>Circadian signaling (MT1 / MT2 receptors)</td>
<td>↓ proliferative circadian disruption</td>
<td>↑ circadian synchronization</td>
<td>Driver</td>
<td>Chronobiology normalization</td>
<td>Melatonin restores circadian control; cancer cells lose growth advantages from circadian dysregulation</td>
</tr>
<tr>
<td>2</td>
<td>Reactive oxygen species (ROS)</td>
<td>↓ ROS (baseline); context-dependent ↑ stress signaling</td>
<td>↓ ROS (strong buffering)</td>
<td>Driver</td>
<td>Antioxidant dominance with signaling effects</td>
<td>Melatonin is a potent direct and indirect antioxidant; cancer cells may still undergo stress-mediated growth inhibition</td>
</tr>
<tr>
<td>3</td>
<td>Mitochondrial function</td>
<td>↓ metabolic flexibility; ↑ apoptosis sensitivity</td>
<td>↑ mitochondrial efficiency</td>
<td>Secondary</td>
<td>Mitochondrial stabilization vs vulnerability</td>
<td>Melatonin improves mitochondrial function in normal cells while limiting metabolic plasticity in cancer cells</td>
</tr>
<tr>
<td>4</td>
<td>Estrogen signaling (ERα modulation)</td>
<td>↓ estrogen-driven proliferation</td>
<td>↔ minimal</td>
<td>Secondary</td>
<td>Hormone-dependent growth suppression</td>
<td>Particularly relevant in breast and hormone-responsive cancers</td>
</tr>
<tr>
<td>5</td>
<td>NF-κB signaling</td>
<td>↓ inflammatory / survival signaling</td>
<td>↓ inflammatory tone</td>
<td>Secondary</td>
<td>Anti-inflammatory modulation</td>
<td>NF-κB suppression contributes to reduced tumor-promoting inflammation</td>
</tr>
<tr>
<td>6</td>
<td>Cell cycle regulation</td>
<td>↓ proliferation / ↑ arrest</td>
<td>↔ spared</td>
<td>Phenotypic</td>
<td>Cytostatic growth control</td>
<td>Growth inhibition reflects upstream circadian and hormonal effects</td>
</tr>
<tr>
<td>7</td>
<td>Apoptosis sensitivity</td>
<td>↑ sensitivity to apoptosis (chemo/RT)</td>
<td>↓ apoptosis</td>
<td>Phenotypic</td>
<td>Therapy sensitization</td>
<td>Melatonin enhances response to chemo- and radiotherapy while protecting normal tissue</td>
</tr>
</table>