Database Query Results : Curcumin, , PARP

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

PARP, poly ADP-ribose polymerase (PARP) cleavage: Click to Expand ⟱

Source:

Type:

Poly (ADP-ribose) polymerase (PARP) cleavage is a hallmark of caspase activation. PARP (Poly (ADP-ribose) polymerase) is a family of proteins involved in a variety of cellular processes, including DNA repair, genomic stability, and programmed cell death. PARP enzymes play a crucial role in repairing single-strand breaks in DNA.
PARP has gained significant attention, particularly in the treatment of certain types of tumors, such as those with BRCA1 or BRCA2 mutations. These mutations impair the cell's ability to repair double-strand breaks in DNA through homologous recombination. Cancer cells with these mutations can become reliant on PARP for survival, making them particularly sensitive to PARP inhibitors.
PARP inhibitors, such as olaparib, rucaparib, and niraparib, have been developed as targeted therapies for cancers associated with BRCA mutations.

PARP Family:
The poly (ADP-ribose) polymerases (PARPs) are a family of enzymes involved in a number of cellular processes, including DNA repair, genomic stability, and programmed cell death.
PARP1 is the predominant family member responsible for detecting DNA strand breaks and initiating repair processes, especially through base excision repair (BER).

PARP1 Overexpression:
In several cancer types—including breast, ovarian, prostate, and lung cancers—elevated PARP1 expression and/or activity has been reported.
High PARP1 expression in certain cancers has been associated with aggressive tumor behavior and resistance to therapies (especially those that induce DNA damage).
Increased PARP1 activity may correlate with poorer overall survival in tumors that rely on DNA repair for survival.

Scientific Papers found: Click to Expand⟱

4671-

CUR,

Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy

in-vitro,

CRC,

CSCs↓, Intriguingly, curcumin and its analogues have also recently been shown to be effective in lowering tumour recurrence by targeting the CSC population, hence inhibiting tumour growth.
TumCG↓,
ChemoSen↑, curcumin could play a role as chemosensitiser whereby the colorectal CSCs are now sensitised towards the anti-cancer therapy,
Wnt↓, Three major signaling pathways in which curcumin plays a pivotal role in CSC self-renewal behavior are the Wnt/β-catenin, Sonic Hedgehog (SHH), and Notch pathways
β-catenin/ZEB1↓,
Shh↓,
NOTCH↓,
DNMT1↓, Figure 1
STAT3↓,
NF-kB↓,
EGFR↓,
IGFR↓,
TumCCA↓,
cl‑PARP↑,
BAX↑,
ECM/TCF↓,

457-

CUR,

Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling

in-vitro,

GC,

SGC-7901

10, 20 and 40 μM, 24 h

in-vitro,

GC,

BGC-823

TumCP↓,
Apoptosis↑,
TumAuto↑,
P53↑,
PI3K↓,
P21↑,
p‑Akt↓,
p‑mTOR↓,
Bcl-2↓,
Bcl-xL↓,
LC3I↓, LC3I
BAX↑,
Beclin-1↑,
cl‑Casp3↑,
cl‑PARP↑,
LC3II↑,
ATG3↑,
ATG5↑,

462-

CUR,

Curcumin promotes cancer-associated fibroblasts apoptosis via ROS-mediated endoplasmic reticulum stress

in-vitro,

Pca,

PC3

10, 20 and 30 μM, 8, 12 and 24 h

Bcl-2↓,
MMP↓,
cl‑Casp3↑,
BAX↑,
BIM↑,
p‑PARP↑,
PUMA↑,
p‑P53↑,
ROS↑,
p‑ERK↑,
p‑eIF2α↑,
CHOP↑,
ATF4↑,

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-Bad
p‑Akt↓,
Akt↓,
cl‑Casp9↑, cleaved
cl‑PARP↑, cleaved

448-

CUR,

Heat shock protein 27 influences the anti-cancer effect of curcumin in colon cancer cells through ROS production and autophagy activation

in-vitro,

CRC,

HT-29

15, 20 and 25 μM, 48 h

Apoptosis↑,
TumCCA↑, G2/M cell cycle arrest
p‑Akt↓,
Akt↓,
Bcl-2↓,
p‑BAD↓,
BAD↑,
cl‑PARP↑,
ROS↑,
HSP27↑,
Beclin-1↑,
p62↑,
GPx1↓,
GPx4↓,

1980-

CUR,

Rad,

Thioredoxin reductase-1 (TxnRd1) mediates curcumin-induced radiosensitization of squamous carcinoma cells

in-vitro,

Cerv,

HeLa

10 µM

in-vitro,

Laryn,

FaDu

10 µM

selectivity↑, previously demonstrated that curcumin radiosensitizes cervical tumor cells without increasing the cytotoxic effects of radiation on normal human fibroblasts
RadioS↑,
TrxR↓, inhibitory activity of curcumin on the anti-oxidant enzyme Thioredoxin Reductase-1 (TxnRd1) is required for curcumin-mediated radiosensitization of squamous carcinoma cells
ROS↑, induced reactive oxygen species
ERK↑, sustained ERK1/2 activation
Dose∅, Curcumin treatment resulted in a dose-dependent decrease in TxnRd activity with an IC50 of approximately 10 µM in both cell lines
cl‑PARP↑, curcumin induced a robust increase in cleaved PARP

475-

CUR,

Curcumin induces apoptotic cell death in human pancreatic cancer cells via the miR-340/XIAP signaling pathway

in-vitro,

PC,

PANC1

2.5, 5, 10 and 20 µM, 72 h

Apoptosis↑,
cl‑Casp3↑,
miR-340↑,
cl‑PARP↑,
XIAP↓,

477-

CUR,

Curcumin induces G2/M arrest and triggers autophagy, ROS generation and cell senescence in cervical cancer cells

in-vitro,

Cerv,

SiHa

5, 15, 30 and 50 µM, 6, 12, 24 and 48 h

TumCP↓,
TumCCA↑, Inducing G2/M cell cycle arrest
Apoptosis↑,
TumAuto↑,
CycB/CCNB1↓, cyclins B1
CDC25↓,
ROS↑,
p62↑,
LC3‑Ⅱ/LC3‑Ⅰ↑,
cl‑Casp3↑,
cl‑PARP↑,
P53↑,
P21↑,

132-

CUR,

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

in-vitro,

Pca,

PC3

TumCCA↑, inducing a chronic ER stress mediated cell death and activation of cell cycle arrest, UPR, autophagy and oxidative stress responses.
ROS↑, correlating with the upregulation of reactive oxygen species
TumAuto↑,
UPR↑, The upregulation of eIF2α in curcumin-treated cells, suggests activation of the UPR-associated PERK pathway
ER Stress↑,
Casp3↑, Chronic ER stress induction was concomitant with the upregulation of pro-apoptotic markers (caspases 3,9,12) and Poly (ADP-ribose) polymerase.
Casp9↑,
Casp12↑,
PARP↑,
other↝, Curcumin-treated PC3 cells expressed 146 upregulated and 184 downregulated proteins when compared with control PC3 cells (treated with DMSO).
GRP78/BiP↑, GRP78 and the PDI family were upregulated by 1.69 and ≥1.25-fold respectively
PDI↑,
eIF2α↑, other upregulated proteins related to ER stress figure eukaryotic translation initiation factor 2A (EIF2A), with a significant fold change of 1.25,
other↝, downregulated antioxidant markers such as peroxiredoxin 6 (PRDX6) and protein DJ-1 (PARK7) with significant fold changes of –1.39 and –1.51, respectively

136-

CUR,

docx,

Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer

in-vitro,

Pca,

DU145

 5-50uM

 19.2 nM(docx), 32.3 μM(CUR)

20 μM curcumin and 10 nM docetaxel significantly decrease (2.7 fold) the proliferation

in-vitro,

Pca,

PC3

 46 nM(docx), 36.1 μM(CUR)

combined treatment decrease (3.2 fold)

Bcl-2↓, combined treatment with curcumin with docetaxel down-regulates the expression of the anti-apoptotic proteins BCL-2, BCL-XL and MCL-1 in DU145 and PC3 cells
Bcl-xL↓,
Mcl-1↓,
BAX↑, Whereas, the expression of the pro-apoptotic markers BAK and BID were significantly up-regulated in curcumin with docetaxel treated group compared to curcumin and docetaxel-treated group alone
BID↑,
PARP↑, combined treatment with curcumin and docetaxel in DU145 and PC3 cells enhanced proteolysis of PARP compared
NF-kB↓, Curcumin blocks NF-κB activation in docetaxel-treated PCa cells
CDK1↓, treatment of curcumin and docetaxel significantly reduced the expression of the proliferation marker CDK-1 and inflammatory marker COX-2
COX2↓,
RTK-RAS↓,
PI3K/Akt↓, combined treatment of curcumin and docetaxel reduced the expression of PI3K, phospho-AKT, EGFR and HER2 in both DU145 and PC3 cells
EGFR↓,
HER2/EBBR2↓, docetaxel in combination with curcumin down-regulates the expression of HER2 and EGFR resulting inhibition of the expression of PI3K kinase and phospho-AKT
P53↑,
ChemoSen↑, The combined treatment of curcumin and docetaxel inhibited the proliferation and induced apoptosis significantly higher than the curcumin and docetaxel-treated group alone.

152-

CUR,

Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer

in-vivo,

Pca,

 PLGA-CUR NPs

 mice

β-catenin/ZEB1↓,
AR↓, Treatment with PLGA-CUR NPs drastically decreases the AR expression level (Figure 5C) compared to free curcumin.
STAT3↓, PLGA-CUR treatment inhibited the expression of STAT3 and phosphorylation of AKT at even the lowest concentration
p‑Akt↓,
Mcl-1↓,
Bcl-xL↓,
cl‑PARP↑, Prostate cancer cells treated with CUR or PLGA-CUR NPs exhibited PARP cleavage and inhibited the expression of anti-apoptotic proteins, Bcl-XL and Mcl-1
miR-21↓, 9-fold reduction in expression of the oncomir, miR-21, in prostate cancer cells (C4-2 and DU-145) t
miR-205↑,
TumCG↓, PLGA-CUR NPs were capable of reducing both in vitro and in vivo prostate cancer cell growth,
TumCP↓, data suggest that curcumin can effectively suppress prostate cancer cell proliferation, invasion, angiogenesis, and metastasis
TumCI↓,
angioG↓,
TumMeta↓,

118-

CUR,

Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells

in-vitro,

Pca,

PC3

 2.2 μM

 for WZ35 analog. For Curcumin it is 20.9μM

in-vitro,

Pca,

DU145

ROS↑, WZ35 treatment for 30 min significantly induced reactive oxygen species (ROS) production in PC-3 cells.
Bcl-2↓,
PARP↑,
cDC2↓, decreased expression of CDC2, cyclinB1, and MDM2
CycB/CCNB1↓,
MDM2↓,
eff↓, Co-treatment with the ROS scavenger NAC completely abrogated the induction of WZ35 on cell apoptosis,
eIF2α↑, WZ35 treatment also induced a constant increase in the level of phosphorylated eIF2α 3 to 12 h after WZ35 treatment
ATF4↑, ATF4 expression also increased in a similar manner with p-eIF2α
CHOP↑, CHOP protein expression apparently increased 9-24 h after WZ35 treatment and peaked at 12 h
ER Stress↑, results suggest that WZ35 can induce ER stress in prostate cancer cells
TumCCA↑, WZ35 induced cell cycle arrest in G2/M phase in PC-3 cells

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↓, 20 microM caused a rapid loss of mitochondrial transmembrane potential
Cyt‑c↑, release of mitochondrial cytochrome c into cytosol
proCasp9↑,
Bcl-2↓,
BAX↑,
PARP↓, degradation of PARP
DNAdam↑,
DFF45↓, through the digestion of DFF-45

150-

NRF,

CUR,

docx,

Subverting ER-Stress towards Apoptosis by Nelfinavir and Curcumin Coexposure Augments Docetaxel Efficacy in Castration Resistant Prostate Cancer Cells

in-vitro,

Pca,

C4-2B

 NFR (5 µM), CUR (5 µM),DTX 10nM

 CRPC

p‑Akt↓,
p‑eIF2α↑, phosphorylated
ER Stress↑, Acute exposure (3–9 hrs) to this 3-drug combination intensified ER-stress induced pro-apoptotic markers, i.e. ATF4, CHOP, and TRIB3.
ATF4↑, 3-drug combination rapidly enhances ER-stress associated death sensors, CHOP, ATF-4 and TRIB3 in C4-2B cells
CHOP↑,
TRIB3↑,
ChemoSen↑, subverting ER-stress towards apoptosis using adjuvant therapy with NFR and CUR can chemosensitize the CRPC cells to DTX therapy.
Casp3↑, NFR or CUR alone could increase Caspase-3 activity in DTX exposed cells
cl‑PARP↑, PARP cleavage assays further confirmed this differential effect of drug combination on apoptotic cell death. In C4-2B cells, a 9-fold increase was observed
BID↑, 3-drug combination rapidly increases ER-stress transducers, BiP, eIF2µ and Xbp-1 in C4-2B cells
XBP-1↑,

* 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:

Total Targets: 0

Scientific Paper Hit Count for: PARP, poly ADP-ribose polymerase (PARP) cleavage

15 Curcumin
2 Docetaxel
1 Radiotherapy/Radiation
1 Garcinol
1 nelfinavir/Viracept

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#:239  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Database Query Results : Curcumin, , PARP

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Pathway results for Effect on Normal Cells:

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