Curcumin / Casp9 Cancer Research Results

CUR, Curcumin: Click to Expand ⟱

Features:

Curcumin is the main active ingredient in Turmeric. 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).

Curcumin — Curcumin is a turmeric-derived polyphenolic curcuminoid and diarylheptanoid from Curcuma longa, functionally best classified as a natural-product small molecule / nutraceutical candidate with pleiotropic redox, inflammatory, transcriptional, metabolic, and chemosensitizing activity. The standard abbreviation is CUR. It is the principal active pigment of turmeric rhizome, usually studied as purified curcumin, curcuminoid mixtures, turmeric extract, phytosomal curcumin, liposomal curcumin, nanoparticle curcumin, or piperine-enhanced formulations. Its oncology relevance is mechanistically broad but clinically constrained by poor aqueous solubility, rapid metabolism, low free systemic exposure, formulation variability, and insufficient well-powered cancer outcome trials.

Primary mechanisms (ranked):

Suppression of NF-κB / STAT3 inflammatory-survival signaling, reducing cytokine, COX-2, iNOS, anti-apoptotic, invasion, and treatment-resistance programs.
Biphasic redox modulation: ROS buffering in normal/inflamed tissue but ROS↑, GSH depletion, thioredoxin reductase disruption, and oxidative stress amplification in susceptible cancer models at sufficient exposure.
Mitochondrial injury and intrinsic apoptosis, including mitochondrial membrane potential loss, cytochrome-c release, caspase activation, PARP cleavage, and ER-stress/UPR involvement.
PI3K/AKT/mTOR and MAPK pathway modulation, contributing to growth arrest, autophagy modulation, apoptosis sensitization, and reduced survival signaling.
Wnt/β-catenin, Hedgehog/GLI, Notch, and cancer-stem-cell suppression, reducing stemness, EMT, invasion, and recurrence-associated phenotypes in models.
Hypoxia / HIF-1α and glycolysis inhibition, including reduced GLUT1, HK2, LDHA, PKM2, lactate/ECAR, and Warburg-like metabolic support in selected models.
Anti-angiogenic and anti-metastatic modulation, including VEGF, MMPs, uPA, CXCR4/SDF-1, TGF-β/α-SMA, FAK, and EMT-related axes.
Epigenetic and transcriptional reprogramming, including reported HDAC, DNMT, EZH2, Sp-family, p53, and microRNA-related effects.
NRF2 modulation: generally cytoprotective in normal cells but potentially protective for cancer cells when NRF2 is activated; NRF2 suppression/knockdown can increase curcumin-induced ROS stress in some tumor models.
Chemosensitization and radiosensitization, with parallel normal-tissue protective signals reported in some mucositis, dermatitis, oxidative-stress, and radioprotection contexts.

Bioavailability / PK relevance: Conventional oral curcumin has poor systemic bioavailability because of low solubility, low absorption, rapid conjugation, and rapid elimination. Oral trials have used doses up to gram-level daily dosing, but circulating free curcumin is typically low; measured plasma exposure often reflects conjugated curcumin. Piperine, phospholipid/phytosome, micellar, liposomal, nanoparticle, and other enhanced formulations can raise exposure, but each formulation should be treated as a distinct translational entity. Delivery constraints are central for oncology interpretation.

In-vitro vs systemic exposure relevance: Common in-vitro anticancer concentrations, often in the low-to-mid micromolar range and sometimes higher, frequently exceed achievable free plasma exposure from standard oral curcumin. Therefore, direct systemic anticancer claims from cell culture should be weighted cautiously unless supported by tissue-local exposure, enhanced formulation data, local delivery, IV/liposomal delivery, or clinically measured pharmacodynamic biomarkers.

Clinical evidence status: Preclinical evidence is extensive; human oncology evidence is mainly small human, biomarker, pilot, chemoprevention, adjunctive, symptom-management, and formulation trials. Current authoritative oncology summaries judge evidence inadequate to recommend curcumin-containing products as cancer treatment or as routine adjunct anticancer therapy, although symptom-support areas such as oral mucositis, radiation dermatitis, oxidative-status measures, and quality of life have more suggestive but still confirmatory-level evidence.

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

Curcumin Cancer Mechanism Ranking

Rank	Pathway / Axis	Cancer Cells	Normal Cells	TSF	Primary Effect	Notes / Interpretation
1	NF-κB / STAT3 inflammatory survival signaling	NF-κB ↓; STAT3 ↓; IL-6/TNF-α/COX-2/iNOS ↓; Bcl-2/Bcl-xL/survivin programs ↓	Inflammatory tone ↓; tissue-protective anti-inflammatory effect likely context-dependent	R/G	Reduced survival, inflammation, invasion, and therapy-resistance signaling	Most central and industry-relevant axis; explains many downstream effects but is not curcumin-specific.
2	Biphasic redox stress and antioxidant buffering	ROS ↑ (dose-dependent); GSH ↓; antioxidant reserve ↓; oxidative apoptosis ↑	ROS ↓; NRF2/SOD/GSH/catalase/HO-1 often ↑ in stress models	R/G	Selective redox pressure in susceptible tumor cells with normal-cell protection in lower-stress settings	Direction depends strongly on concentration, formulation, light exposure, basal redox state, and tumor antioxidant capacity.
3	Thioredoxin reductase and GSH linked redox systems	TrxR inhibition or redox cycling ↑; GSH depletion ↑; oxidative stress ↑	Usually buffered or antioxidant response ↑ at non-toxic exposure	R/G	Collapse of tumor redox compensation	Mechanistically important for ROS amplification and radiosensitization; achievable exposure remains a major constraint.
4	Mitochondrial depolarization and intrinsic apoptosis	ΔΨm ↓; cytochrome-c ↑; caspase-3/9 ↑; PARP cleavage ↑; apoptosis ↑	Generally ↔ or protected under oxidative/inflammatory stress	R/G	Execution of apoptosis after upstream redox and survival-signal disruption	Central cytotoxic endpoint in many cell models; often downstream of ROS, ER stress, AKT/mTOR suppression, or p53 modulation.
5	PI3K / AKT / mTOR and autophagy balance	PI3K ↓; AKT ↓; mTOR ↓; survival signaling ↓; autophagy ↑ or mixed	Stress-adaptive autophagy ↔ or ↑ (context-dependent)	R/G	Growth suppression and apoptosis sensitization	Autophagy may be cytotoxic or protective depending on model and timing; combination logic may require autophagy-state interpretation.
6	Wnt / β-catenin / Hedgehog / Notch stemness signaling	β-catenin ↓; GLI/Hedgehog ↓; Notch ↓; CD133/CD44/OCT4/SOX2-like stemness markers ↓	Generally ↔; possible normal stem-cell effects are tissue/context-dependent	G	Reduced cancer stemness, EMT, self-renewal, and recurrence-associated phenotypes	Important for anti-metastatic and anti-CSC positioning; evidence is mainly preclinical.
7	HIF-1α / glycolysis / Warburg metabolism	HIF-1α ↓; GLUT1 ↓; HK2 ↓; LDHA ↓; PKM2 ↓; lactate/ECAR ↓; ATP stress ↑	Metabolic effects ↔ or adaptive; normal-cell toxicity depends on exposure	G	Reduced hypoxic adaptation and glycolytic energy support	Mechanistically relevant but formulation and tissue exposure are critical; hypoxic tumors may be more relevant than normoxic cell culture.
8	EMT / invasion / metastasis matrix axis	EMT ↓; MMP2/MMP9 ↓; uPA ↓; FAK ↓; CXCR4/SDF-1 ↓; migration/invasion ↓	Inflammation-linked remodeling ↓; wound-healing effects context-dependent	G	Anti-invasive and anti-metastatic phenotype	Strongly supported in models; clinical anti-metastatic efficacy is not established.
9	VEGF / angiogenesis / hypoxia interface	VEGF ↓; HIF-1α ↓; angiogenic signaling ↓	Angiogenesis modulation ↔ or ↓ (context-dependent)	G	Reduced tumor vascular-support signaling	Overlaps with NF-κB, HIF-1α, STAT3, and inflammatory cytokine suppression.
10	Epigenetic and transcriptional reprogramming	HDAC ↓; DNMT1/3A ↓; EZH2 ↓; Sp proteins ↓; p53 ↑ or restored in selected models	Broad transcriptional effects possible; selectivity uncertain	G	Reactivation of growth-control and differentiation-associated programs	Biologically plausible but highly model-dependent; direct target specificity is lower than pathway-level interpretation.
11	Ferroptosis and iron redox stress	Iron/redox stress ↑; lipid peroxidation ↑; GPX4/GSH axis may ↓ (model-dependent)	Iron-chelation and antioxidant protection may occur (context-dependent)	R/G	Potential ferroptosis contribution in susceptible tumor models	Curcumin can behave as an iron chelator, antioxidant, or pro-oxidant depending on exposure, formulation, and cancer redox context.
12	NRF2 cytoprotection risk	NRF2 ↑ may protect tumor cells; NRF2 depletion can enhance curcumin-induced ROS stress in some models	NRF2 ↑ supports antioxidant and anti-inflammatory tissue protection	G	Dual-edged stress-response modulation	Important caution for antioxidant matrix use: NRF2 activation is favorable in normal-cell protection but may be undesirable in NRF2-addicted tumors.
13	Chemosensitization and radiosensitization	Chemo response ↑; radiation response ↑; apoptosis ↑; resistance pathways ↓	Chemo/radiation injury may ↓ in mucositis, dermatitis, and oxidative-stress contexts	R/G	Adjunct sensitization with possible normal-tissue protection	Attractive translational axis, but clinical evidence remains mainly pilot/small-study; interaction risk should be checked per regimen.
14	Clinical Translation Constraint	Free systemic exposure often insufficient for direct cytotoxic extrapolation from in-vitro micromolar data	Enhanced formulations may improve exposure but may also alter safety, liver-risk profile, and interaction potential	G	Bioavailability and formulation dominate translational interpretation	Separate ordinary curcumin, turmeric extract, piperine-enhanced, phytosomal, micellar, liposomal, nanoparticle, and IV/liposomal products where possible.

TSF legend:

P: 0–30 min

R: 30 min–3 hr

G: >3 hr

Casp9, Caspase-9: Click to Expand ⟱

Source:

Type:

Caspase-9 is the apoptotic initiator protease of the intrinsic or mitochondrial apoptotic pathway, which is activated at multi-protein activation platforms.
Caspases are divided into two groups: the initiator caspases (caspase-2, -8, -9 and -10), which are the first to be activated in response to a signal, and the executioner caspases (caspase-3, -6, and -7) that carry out the demolition phase of apoptosis.
Caspase-9:
Role: Initiator caspase in the intrinsic apoptotic pathway.
Cancers: Frequently studied in leukemia and solid tumors.
Prognosis: Reduced expression is often linked to chemoresistance and poor prognosis.

Scientific Papers found: Click to Expand⟱

4652-

CUR,

Anticancer effect of curcumin on breast cancer and stem cells

Review,

BC,

TumCP↓, TumMeta↓, TumCCA↑, Apoptosis↑, CSCs↓, NF-kB↓, Telomerase↓, Cyt‑c↑, Casp9↑, Casp3↑, E-cadherin↑,

6219-

CUR,

Natural Products and Altered Metabolism in Cancer: Therapeutic Targets and Mechanisms of Action

Review,

Var,

PI3K↓, Akt↓, NF-kB↓, BioAv↑, GSK‐3β↓, Slug↓, Cyt‑c↑, Casp3↑, Casp9↑,

6214-

CUR,

Curcumin Nanoparticles-related Non-invasive Tumor Therapy, and Cardiotoxicity Relieve

TumCD↓, TumCI↓, *Inflam↓, *antiOx↓, *AntiTum↓, NF-kB↓, COX2↓, Casp9↓, ROS↑, BioAv↑, RadioS↑, ChemoSen↑, Imm↑, PhotoS↑, sonoS↑, 5LO↓, iNOS↓, IL2↓, TNF-α↓, Casp9↑, Casp3↑, Bcl-2↓, BAX↑, Apoptosis↑, ER Stress↑, cycD1/CCND1↓, CDK2↓, CycB/CCNB1↓, TumCCA↑, MMPs↓, *radioP↑, chemoP↑, hepatoP↑, cardioP↑, eff↑, PhotoS↑, eff↑, ROS↑, GSH↓,

471-

CUR,

Curcumin induces apoptotic cell death and protective autophagy by inhibiting AKT/mTOR/p70S6K pathway in human ovarian cancer cells

in-vitro,

Ovarian,

SKOV3

5, 10, 20, 40 and 80 μM, 24, 48 and 72 h

in-vitro,

Ovarian,

A2780S

Apoptosis↑, TumAuto↑, p62↓, p‑Akt↓, p‑mTOR↓, p‑P70S6K↓, Casp9↑, PARP↑, ATG3↑, Beclin-1↑, LC3‑Ⅱ/LC3‑Ⅰ↑,

434-

CUR,

Curcumin induces apoptosis in lung cancer cells by 14-3-3 protein-mediated activation of Bad

in-vitro,

Lung,

A549

25, 50 and 100 μM, 48h

14-3-3 proteins↓, p‑BAD↓, p‑Akt↓, Akt↓, cl‑Casp9↑, cl‑PARP↑,

484-

CUR,

PDT,

Low concentrations of curcumin induce growth arrest and apoptosis in skin keratinocytes only in combination with UVA or visible light

in-vitro,

Melanoma,

0.2-1 microg/ml

skin keratinocytes

Cyt‑c↑, Casp9↑, Casp8↑, NF-kB↓, EGFR↓,

485-

CUR,

PDT,

Red Light Combined with Blue Light Irradiation Regulates Proliferation and Apoptosis in Skin Keratinocytes in Combination with Low Concentrations of Curcumin

in-vitro,

Melanoma,

1.25–3.12 μM

Skin Keratinocytes

NF-kB↓, Casp8↑, Casp9↑, p‑Akt↓, p‑ERK↓,

132-

CUR,

Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells

in-vitro,

Pca,

PC3

TumCCA↑, ROS↑, TumAuto↑, UPR↑, ER Stress↑, Casp3↑, Casp9↑, Casp12↑, PARP↑, other↝, GRP78/BiP↑, PDI↑, eIF2α↑, other↝,

137-

CUR,

Curcumin induces G0/G1 arrest and apoptosis in hormone independent prostate cancer DU-145 cells by down regulating Notch signaling

in-vitro,

Pca,

DU145

NOTCH1↓, cycD1/CCND1↓, CDK2↓, P21↑, p27↑, P53↑, Bcl-2↓, Casp3↑, Casp9↑, TumCCA↑, TumCP↓, Apoptosis↑,

417-

CUR,

Curcumin inhibits the growth of triple‐negative breast cancer cells by silencing EZH2 and restoring DLC1 expression

vitro+vivo,

BC,

MCF-7

20 and 40 µM, 48 h; 100 mg/kg/2 days, 21 days

mice

vitro+vivo,

BC,

MDA-MB-231

vitro+vivo,

BC,

MDA-MB-468

EZH2↓, DLC1↑, cycA1/CCNA1↓, CDK1↓, Bcl-2↓, Casp9↑, DLC1↑,

167-

CUR,

Curcumin-induced apoptosis in PC3 prostate carcinoma cells is caspase-independent and involves cellular ceramide accumulation and damage to mitochondria

in-vitro,

Pca,

PC3

MAPK↑, JNK↑, Casp3↑, Casp8↑, Casp9↑, AIF↑, GSH↓, eff↓, Apoptosis↑, DNAdam↑,

159-

CUR,

Crosstalk from survival to necrotic death coexists in DU-145 cells by curcumin treatment

in-vitro,

Pca,

DU145

ROS↑, p‑Jun↑, p‑p38↑, TumAuto↑, Casp8↑, Casp9↑, Akt↓, ERK↓, p38↓,

808-

GAR,

CUR,

Synergistic effect of garcinol and curcumin on antiproliferative and apoptotic activity in pancreatic cancer cells

in-vitro,

PC,

Bxpc-3

10uM(Gar), 5uM(Cur)

combination of garcinol and curcumin was 2 to 10 fold that of the individual agents

in-vitro,

PC,

PANC1

tumCV↓, Apoptosis↑, Casp3↑, Casp9↑,

831-

GAR,

CUR,

Induction of apoptosis by garcinol and curcumin through cytochrome c release and activation of caspases in human leukemia HL-60 cells

in-vitro,

AML,

HL-60

20 microM

9.4uM(Gar), 19.5uM(Cur)

Apoptosis↑, Casp3↑, MMP↓, Cyt‑c↑, proCasp9↑, Bcl-2↓, BAX↑, PARP↓, DNAdam↑, DFF45↓,

103-

RES,

CUR,

QC,

The effect of resveratrol, curcumin and quercetin combination on immuno-suppression of tumor microenvironment for breast tumor-bearing mice

vitro+vivo,

BC,

4T1

 Mice: 24 mg/kg
Res, 24 mg/kg
Cur, 12 mg/kg
Que
Translated into an edible human dose of 738 mg/day (including 295.2 mg Res, 295.2 mg Cur, and 147.6 mg Que)

 8.5mg/L

 mice

ROS↑, MMP↓, Bcl-2↓, BAX↑, Casp9↑, T-Cell↑, TGF-β↓,

Showing Research Papers: 1 to 15 of 15

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↓, 1,

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,

Functional Outcomes ⓘ

AntiTum↓, 1, radioP↑, 1,
Total Targets: 4

Scientific Paper Hit Count for: Casp9, Caspase-9

15 Curcumin
2 Photodynamic Therapy
2 Garcinol
1 Resveratrol
1 Quercetin

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#:65  Target#:45  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

Curcumin / Casp9 Cancer Research Results

Curcumin Cancer Mechanism Ranking

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Immune & Inflammatory Signaling ⓘ

Functional Outcomes ⓘ

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