Curcumin / Casp3 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


Casp3, CPP32, Cysteinyl aspartate specific proteinase-3: Click to Expand ⟱
Source:
Type:
Also known as CP32.
Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death.
As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.
On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.
Procaspase-3 is a apoptotic marker protein.
Prognostic significance:
• High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.
• Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.
Scientific Papers found: Click to Expand⟱
2818- CUR,    Novel Insight to Neuroprotective Potential of Curcumin: A Mechanistic Review of Possible Involvement of Mitochondrial Biogenesis and PI3/Akt/ GSK3 or PI3/Akt/CREB/BDNF Signaling Pathways
- Review, AD, NA
*neuroP↑, *ROS↓, *Inflam↓, *Apoptosis↓, *cognitive↑, *cardioP↑, other↑, *COX2↓, *IL1β↓, *TNF-α↓, NF-kB↓, *PGE2↓, *iNOS↓, *NO↓, *IL2↓, *IL4↓, *IL6↓, *INF-γ↓, *GSK‐3β↓, *STAT↓, *GSH↑, *MDA↓, *lipid-P↓, *SOD↑, *GPx↑, *Catalase↑, *GSR↓, *LDH↓, *H2O2↓, *Casp3↓, *Casp9↓, *NRF2↑, *AIF↓, *ATP↑,
3580- CUR,    Curcumin Acts as Post-protective Effects on Rat Hippocampal Synaptosomes in a Neuronal Model of Aluminum-Induced Toxicity
- in-vivo, AD, NA
*ROS↓, *Cyt‑c↓, *Casp3↓, *neuroP↑,
461- CUR,    Curcumin inhibits prostate cancer progression by regulating the miR-30a-5p/PCLAF axis
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145
TumCP↓, TumCMig↓, TumCI↓, Apoptosis↑, miR-30a-5p↑, PCLAF↓, Bcl-2↓, Casp3↓, BAX↑, cl‑Casp3↑,
452- CUR,    Curcumin downregulates the PI3K-AKT-mTOR pathway and inhibits growth and progression in head and neck cancer cells
- vitro+vivo, HNSCC, SCC9 - vitro+vivo, HNSCC, FaDu - vitro+vivo, HNSCC, HaCaT
TumCCA↑, PI3k/Akt/mTOR↓, Casp3↑, EGFR↓, EGF↑, PRKCG↑, p‑Akt↓, p‑mTOR↓, RPS6KA1↓, EIF4E↓, proCasp3↓,
2133- TQ,  CUR,  Cisplatin,    Thymoquinone and curcumin combination protects cisplatin-induced kidney injury, nephrotoxicity by attenuating NFκB, KIM-1 and ameliorating Nrf2/HO-1 signalling
- in-vitro, Nor, HEK293 - in-vivo, NA, NA
*creat↓, *TNF-α↓, *IL6↓, *MRP↓, *GFR↑, *mt-ATPase↑, *p‑Akt↑, *NRF2↑, *HO-1↑, *Casp3↓, *NF-kB↓, *RenoP↑,

Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Mitochondria & Bioenergetics ⓘ

EGF↑, 1,  

Core Metabolism/Glycolysis ⓘ

PI3k/Akt/mTOR↓, 1,  

Cell Death ⓘ

p‑Akt↓, 1,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↓, 1,   Casp3↑, 1,   cl‑Casp3↑, 1,   proCasp3↓, 1,  

Transcription & Epigenetics ⓘ

miR-30a-5p↑, 1,   other↑, 1,  

DNA Damage & Repair ⓘ

PCLAF↓, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EIF4E↓, 1,   p‑mTOR↓, 1,   PRKCG↑, 1,   RPS6KA1↓, 1,  

Migration ⓘ

TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,  
Total Targets: 24

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   GSR↓, 1,   H2O2↓, 1,   HO-1↑, 1,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 2,   ROS↓, 2,   SOD↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↓, 1,   ATP↑, 1,  

Core Metabolism/Glycolysis ⓘ

LDH↓, 1,  

Cell Death ⓘ

p‑Akt↑, 1,   Apoptosis↓, 1,   Casp3↓, 3,   Casp9↓, 1,   Cyt‑c↓, 1,   iNOS↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1,   STAT↓, 1,  

Migration ⓘ

mt-ATPase↑, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Barriers & Transport ⓘ

MRP↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL1β↓, 1,   IL2↓, 1,   IL4↓, 1,   IL6↓, 2,   INF-γ↓, 1,   Inflam↓, 1,   NF-kB↓, 1,   PGE2↓, 1,   TNF-α↓, 2,  

Clinical Biomarkers ⓘ

creat↓, 1,   IL6↓, 2,   LDH↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   cognitive↑, 1,   GFR↑, 1,   neuroP↑, 2,   RenoP↑, 1,  
Total Targets: 43

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
5 Curcumin
1 Thymoquinone
1 Cisplatin
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#:42  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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