Melatonin / HDAC1 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


HDAC1, Histone Deacetylase 1: Click to Expand ⟱
Source:
Type:
HDAC1 is an enzyme that removes acetyl groups from histone tails, resulting in chromatin condensation and transcriptional repression.
– By modulating the acetylation status of histones, HDAC1 plays a key role in regulating gene expression involved in cell cycle progression, differentiation, apoptosis, and DNA repair.
– Aberrant expression or activity of HDAC1 has been linked to several cancers.
– Overexpression of HDAC1 can lead to the repression of tumor suppressor genes, thereby promoting oncogenic programs and contributing to tumor progression.
– HDAC1 is often associated with a more aggressive tumor phenotype and, in some contexts, a poorer clinical prognosis.
Therapeutic Targeting:
– HDAC inhibitors (HDACis) have emerged as anticancer agents; they work by inhibiting HDAC activity to restore acetylation levels on histones and nonhistone proteins.
Scientific Papers found: Click to Expand⟱
1063- MEL,    HDAC1 inhibition by melatonin leads to suppression of lung adenocarcinoma cells via induction of oxidative stress and activation of apoptotic pathways
- in-vitro, Lung, A549 - in-vitro, Lung, PC9
AntiCan↑, TumCMig↓, GSH↓, Casp3↑, Apoptosis↑, ROS↑, HDAC1↓, Ac-histone H3↑, PUMA↑, BAX↑, PCNA↓, Bcl-2↓,

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 ⓘ

GSH↓, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis ⓘ

Ac-histone H3↑, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   PUMA↑, 1,  

DNA Damage & Repair ⓘ

PCNA↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

HDAC1↓, 1,  

Migration ⓘ

TumCMig↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,  
Total Targets: 12

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: HDAC1, Histone Deacetylase 1
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#:982  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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