Curcumin / EP300 Cancer Research Results

CUR, Curcumin: Click to Expand ⟱

Features:

Curcumin is the main active ingredient in Tumeric. Member of the ginger family.Curcumin is a polyphenol extracted from turmeric with anti-inflammatory and antioxidant properties.
- Has iron-chelating, iron-chelating properties. Ferritin. But still known to increase Iron in Cancer cells.
- GSH depletion in cancer cells, exhaustion of the antioxidant defense system. But still raises GSH↑ in normal cells.
- Higher concentrations (5-10 μM) of curcumin induce autophagy and ROS production
- Inhibition of TrxR, shifting the enzyme from an antioxidant to a prooxidant
- Strong inhibitor of Glo-I, , causes depletion of cellular ATP and GSH
- Curcumin has been found to act as an activator of Nrf2, (maybe bad in cancer cells?), hence could be combined with Nrf2 knockdown
-may suppress CSC: suppresses self-renewal and pathways (Wnt/Notch/Hedgehog).
Clinical studies testing curcumin in cancer patients have used a range of dosages, often between 500 mg and 8 g per day; however, many studies note that doses on the lower end may not achieve sufficient plasma concentrations for a therapeutic anticancer effect in humans.
• Formulations designed to improve curcumin absorption (like curcumin combined with piperine, nanoparticle formulations, or liposomal curcumin) are often employed in clinical trials to enhance its bioavailability.

-Note half-life 6 hrs.
BioAv is poor, use piperine or other enhancers
Pathways:
- induce ROS production at high concentration. Lowers ROS at lower concentrations
curcumin can act as a pro-oxidant when blue light is applied
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: GSH↓ Catalase↓ HO1↓ GPx↓
but conversely is known as a NRF2↑ activator in cancer
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, uPA↓, VEGF↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, HK2↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, GLi1↓, CD133↓, CD24↓, β-catenin↓, n-myc↓, sox2↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK, TrxR**,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank	Pathway / Axis	Cancer Cells	Normal Cells	Label	Primary Interpretation	Notes
1	NF-κB signaling	↓ NF-κB activation	↓ inflammatory NF-κB tone	Driver	Suppression of survival and inflammatory transcription	NF-κB is a primary, repeatedly validated curcumin target explaining pleiotropic downstream effects
2	STAT3 signaling	↓ STAT3 phosphorylation / activity	↔ or mild suppression	Driver	Loss of pro-survival and proliferative signaling	STAT3 inhibition contributes to growth arrest, apoptosis sensitization, and reduced cytokine signaling in tumors
3	Reactive oxygen species (ROS)	↑ ROS (dose- & context-dependent)	↓ ROS / buffered	Conditional Driver	Biphasic redox modulation	Curcumin can act as a pro-oxidant in cancer cells with high basal stress while acting antioxidant in normal cells
4	Mitochondrial integrity / intrinsic apoptosis	↓ ΔΨm; ↑ caspase activation	↔ preserved	Driver	Execution of intrinsic apoptosis	Mitochondrial dysfunction and caspase activation occur downstream of NF-κB/STAT3 and ROS effects
5	PI3K → AKT → mTOR axis	↓ AKT / ↓ mTOR	↔ or adaptive suppression	Secondary	Reduced growth and anabolic signaling	AKT/mTOR inhibition contributes to growth suppression and autophagy induction in cancer cells
6	Autophagy	↑ autophagy (protective or pro-death)	↑ adaptive autophagy	Secondary	Stress adaptation vs cell death	Autophagy may be cytoprotective or cooperate with apoptosis depending on context and dose
7	HIF-1α / VEGF hypoxia–angiogenesis axis	↓ HIF-1α; ↓ VEGF	↔ minimal effect	Secondary	Anti-angiogenic pressure	Suppression of hypoxia-driven transcription limits angiogenesis and tumor adaptation
8	Cell cycle regulation	↑ G2/M or G1 arrest	↔ largely spared	Phenotypic	Cytostatic growth control	Cell-cycle arrest reflects upstream signaling and epigenetic effects rather than direct CDK inhibition
9	Migration / invasion (EMT, MMP axis)	↓ migration & invasion	↔	Phenotypic	Anti-metastatic phenotype	Reduced EMT markers and protease activity limit invasive behavior
10	Epigenetic regulation (p300/CBP HAT activity)	↓ histone acetylation	↔ modest	Secondary	Transcriptional reprogramming	Curcumin modulates chromatin via HAT inhibition rather than classic HDAC inhibition

EP300, E1A binding protein p300: Click to Expand ⟱

Source: CGL-Driver Genes

Type: TSG (actually onocogene)

A transcriptional co-activator that plays a crucial role in regulating gene expression, cell growth, and differentiation. It is involved in various cellular processes, including the response to signaling pathways and the regulation of the cell cycle.
EP300 functions as a tumor suppressor in some contexts, while in others, it may promote oncogenic processes. Its role can depend on the specific type of cancer and the molecular context.
High levels may correlate with poor survival outcomes.
EP300 is a critical player in cancer biology, with its expression levels serving as potential biomarkers for prognosis in various cancers. Its role in transcriptional regulation and chromatin remodeling underscores its importance in tumorigenesis and cancer progression.

EP300 (p300) encodes a histone acetyltransferase (HAT) and transcriptional co-activator. p300 acetylates histones (e.g., H3, H4) and numerous non-histone proteins, loosening chromatin and enabling transcription. It functions as a signal integrator, translating upstream cues (growth factors, stress, hypoxia) into gene expression programs.

Key Pathways Modulated by EP300
Pathway / TF	           EP300 Effect	                Cancer Consequence
p53	                   Acetylation → activation	Tumor suppression (when intact)
MYC	                   Co-activation	        Proliferation, metabolism
HIF-1α	                   Co-activation under hypoxia	Angiogenesis, survival
NF-κB	                   Acetylation	                Inflammation, survival
Hormone receptors (ER/AR)  Co-activation	        Lineage-specific growth

Scientific Papers found: Click to Expand⟱

415-

CUR,

Curcumin inhibits proteasome activity in triple-negative breast cancer cells through regulating p300/miR-142-3p/PSMB5 axis

vitro+vivo,

BC,

MDA-MB-231

5, 10, 20 and 50 μM, 24 h; 25 g/kg, 4 weeks

mice

PSMB5↓, CT-I↓, miR-142-3p↑, EP300↓,

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:

Core Metabolism/Glycolysis ⓘ

PSMB5↓, 1,

Proliferation, Differentiation & Cell State ⓘ

EP300↓, 1, miR-142-3p↑, 1,

Drug Metabolism & Resistance ⓘ

CT-I↓, 1,
Total Targets: 4

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: EP300, E1A binding protein p300

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