Melatonin / CHOP 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


CHOP, GADD153: Click to Expand ⟱
Source:
Type: Protein
GADD153 and CHOP (C/EBP-homologous protein) refer to the same protein. GADD153 stands for "Growth Arrest and DNA Damage-inducible protein 153," while CHOP stands for "C/EBP Homologous Protein."
DDIT3 (DNA Damage Inducible Transcript 3), also known as CHOP (C/EBP Homologous Protein), is a transcription factor that plays a significant role in the cellular response to stress, particularly in the context of the unfolded protein response (UPR) and apoptosis.

CHOP is an important component of the endoplasmic reticulum (ER) stress response. Research has shown that knockdown of CHOP not only enhances tunicamycin-induced autophagy, but also significantly attenuates ER stress-induced apoptosis in human colon cancer cells.
GADD153, also known as CHOP (C/EBP homologous protein), is a transcription factor that plays a significant role in cellular stress responses, particularly in the context of the endoplasmic reticulum (ER) stress response. It is part of the unfolded protein response (UPR), which is activated when there is an accumulation of misfolded proteins in the ER.
Scientific Papers found: Click to Expand⟱
1351- And,  MEL,    Impact of Andrographolide and Melatonin Combinatorial Drug Therapy on Metastatic Colon Cancer Cells and Organoids
- in-vitro, CRC, T84 - in-vitro, CRC, COLO205 - in-vitro, CRC, HT-29 - in-vitro, CRC, DLD1
eff↑, Ki-67↓, Casp3↑, ER Stress↑, ROS↑, BAX↑, XBP-1↑, CHOP↑, 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 ⓘ

BAX↑, 1,   Casp3↑, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 1,   XBP-1↑, 1,  

Migration ⓘ

Ki-67↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 2,  

Clinical Biomarkers ⓘ

Ki-67↓, 1,  
Total Targets: 9

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: CHOP, GADD153
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#:490  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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