Curcumin / Casp9 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


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, NA
TumCP↓, TumMeta↓, TumCCA↑, Apoptosis↑, CSCs↓, NF-kB↓, Telomerase↓, Cyt‑c↑, Casp9↑, Casp3↑, E-cadherin↑,
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 - 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
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, NA
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, NA
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 - 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 - 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
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
ROS↑, MMP↓, Bcl-2↓, BAX↑, Casp9↑, T-Cell↑, TGF-β↓,

Showing Research Papers: 1 to 13 of 13

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 13

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 1,   ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   MMP↓, 2,  

Cell Death ⓘ

14-3-3 proteins↓, 1,   Akt↓, 2,   p‑Akt↓, 3,   Apoptosis↑, 6,   p‑BAD↓, 1,   BAX↑, 2,   Bcl-2↓, 4,   Casp12↑, 1,   Casp3↑, 6,   Casp8↑, 4,   Casp9↑, 11,   cl‑Casp9↑, 1,   proCasp9↑, 1,   Cyt‑c↑, 3,   JNK↑, 1,   MAPK↑, 1,   p27↑, 1,   p38↓, 1,   p‑p38↑, 1,   Telomerase↓, 1,  

Transcription & Epigenetics ⓘ

EZH2↓, 1,   other↝, 2,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

eIF2α↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

ATG3↑, 1,   Beclin-1↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   p62↓, 1,   TumAuto↑, 3,  

DNA Damage & Repair ⓘ

DFF45↓, 1,   DNAdam↑, 2,   P53↑, 1,   PARP↓, 1,   PARP↑, 2,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 1,   cycA1/CCNA1↓, 1,   cycD1/CCND1↓, 1,   P21↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   ERK↓, 1,   p‑ERK↓, 1,   p‑Jun↑, 1,   p‑mTOR↓, 1,   NOTCH1↓, 1,   p‑P70S6K↓, 1,  

Migration ⓘ

DLC1↑, 2,   E-cadherin↑, 1,   TGF-β↓, 1,   TumCP↓, 2,   TumMeta↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   PDI↑, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 3,   T-Cell↑, 1,  

Drug Metabolism & Resistance ⓘ

eff↓, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   EZH2↓, 1,  
Total Targets: 67

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Casp9, Caspase-9
13 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

 

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