Melatonin / DR5 Cancer Research Results

MEL, Melatonin: Click to Expand ⟱
Features:
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
Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Circadian signaling (MT1 / MT2 receptors) ↓ proliferative circadian disruption ↑ circadian synchronization Driver Chronobiology normalization Melatonin restores circadian control; cancer cells lose growth advantages from circadian dysregulation
2 Reactive oxygen species (ROS) ↓ ROS (baseline); context-dependent ↑ stress signaling ↓ ROS (strong buffering) Driver Antioxidant dominance with signaling effects Melatonin is a potent direct and indirect antioxidant; cancer cells may still undergo stress-mediated growth inhibition
3 Mitochondrial function ↓ metabolic flexibility; ↑ apoptosis sensitivity ↑ mitochondrial efficiency Secondary Mitochondrial stabilization vs vulnerability Melatonin improves mitochondrial function in normal cells while limiting metabolic plasticity in cancer cells
4 Estrogen signaling (ERα modulation) ↓ estrogen-driven proliferation ↔ minimal Secondary Hormone-dependent growth suppression Particularly relevant in breast and hormone-responsive cancers
5 NF-κB signaling ↓ inflammatory / survival signaling ↓ inflammatory tone Secondary Anti-inflammatory modulation NF-κB suppression contributes to reduced tumor-promoting inflammation
6 Cell cycle regulation ↓ proliferation / ↑ arrest ↔ spared Phenotypic Cytostatic growth control Growth inhibition reflects upstream circadian and hormonal effects
7 Apoptosis sensitivity ↑ sensitivity to apoptosis (chemo/RT) ↓ apoptosis Phenotypic Therapy sensitization Melatonin enhances response to chemo- and radiotherapy while protecting normal tissue


DR5, Death receptor 5: Click to Expand ⟱
Source:
Type:
A protein reported to play an important role in sensitizing cancer cells to apoptosis. Death Receptor 5 (DR5), also known as TRAIL receptor 2, is a member of the tumor necrosis factor (TNF) receptor superfamily. It plays a crucial role in the apoptosis (programmed cell death) pathway, particularly in the context of cancer.
DR5 is often overexpressed in various types of tumors, including breast, colon, and lung cancers. This overexpression can make cancer cells more susceptible to TRAIL-induced apoptosis.
Scientific Papers found: Click to Expand⟱
1777- MEL,    Melatonin as an antioxidant: under promises but over delivers
- Review, NA, NA
*ROS↓, *Fenton↓, *antiOx↑, *toxicity∅, *GPx↑, *GSR↑, *GSH↑, *NO↓, *Iron↓, *Copper↓, *IL1β↓, *iNOS↓, *Casp3↓, *BBB↑, *RenoP↑, chemoP↑, *Ca+2↝, eff↑, *PKCδ?, ChemoSen↑, eff↑, Akt↓, DR5↑, selectivity↑, ROS↑, eff↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 1,  

Cell Death ⓘ

Akt↓, 1,   DR5↑, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 3,   selectivity↑, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,  
Total Targets: 7

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Copper↓, 1,   Fenton↓, 1,   GPx↑, 1,   GSH↑, 1,   GSR↑, 1,   Iron↓, 1,   ROS↓, 1,  

Cell Death ⓘ

Casp3↓, 1,   iNOS↓, 1,  

Migration ⓘ

Ca+2↝, 1,   PKCδ?, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,  

Functional Outcomes ⓘ

RenoP↑, 1,   toxicity∅, 1,  
Total Targets: 17

Scientific Paper Hit Count for: DR5, Death receptor 5
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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:122  Target#:88  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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