Curcumin / angioS 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

angioS, angiostatin: Click to Expand ⟱

Source:

Type:

Angiostatin, a key protein that suppresses angiogenesis. Angiostatin may be used in anti-angiogenesis therapy. A protein that blocks angiogenesis (the growth of new blood vessels) and is involved in blood clotting.
Angiostatin is a protein that is known to inhibit angiogenesis, the process by which new blood vessels form from existing ones. It is derived from the cleavage of plasminogen and has been studied for its potential role in cancer biology, particularly in relation to tumor growth and metastasis.

Angiostatin in Cancer
Mechanism of Action: Angiostatin inhibits endothelial cell proliferation and migration, which are critical steps in angiogenesis. By preventing the formation of new blood vessels, angiostatin can limit the supply of nutrients and oxygen to tumors, potentially slowing their growth.

The expression levels of angiostatin in tumors have been associated with patient prognosis in some studies. Higher levels of angiostatin may correlate with better outcomes in certain cancers, as they may indicate a more effective anti-angiogenic response. Conversely, low levels of angiostatin might be associated with poor prognosis and more aggressive disease.

Scientific Papers found: Click to Expand⟱

155-

CUR,

Osteopontin and MMP9: Associations with VEGF Expression/Secretion and Angiogenesis in PC3 Prostate Cancer Cells

in-vitro,

Pca,

PC3

p‑ERK↓, VEGF↓, angioG↓, MMP2↓, MMP9↓, angioS↑,

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:

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↓, 1,

Migration ⓘ

MMP2↓, 1, MMP9↓, 1,

Angiogenesis & Vasculature ⓘ

angioG↓, 1, angioS↑, 1, VEGF↓, 1,
Total Targets: 6

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: angioS, angiostatin

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