Database Query Results : Curcumin, , Akt

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

Akt, PKB-Protein kinase B: Click to Expand ⟱

Source: HalifaxProj(inhibit)

Type:

Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes; Akt2 is an important signaling molecule in the insulin signaling pathway. It is required to induce glucose transport.

Inhibitors:
-Curcumin: downregulate AKT phosphorylation and signaling.
-Resveratrol
-Quercetin: inhibit the PI3K/AKT pathway.
-Epigallocatechin Gallate (EGCG)
-Luteolin and Apigenin: inhibit AKT phosphorylation

Scientific Papers found: Click to Expand⟱

3861-

CUR,

Curcumin as a novel therapeutic candidate for cancer: can this natural compound revolutionize cancer treatment?

Review,

Var,

*antiOx↑, fig 1
*Inflam↓,
PI3K↓, By inhibiting pro-survival and pro-inflammatory signaling cascades such as PI3K/Akt/mTOR, MAPK, Wnt/β-catenin, NF-κB, Hedgehog, Notch, and JAK/STAT3, curcumin effectively impedes cancer cell growth and promotes apoptosis.
Akt↓,
mTOR↓,
Wnt↓,
β-catenin/ZEB1↓,
NF-kB↓,
HH↓,
NOTCH↓,
JAK↓,
STAT3↓,
ADAM10↓, Curcumin may inhibit the function of the Notch pathway in cancer by inhibiting Notch pathway activators such as gamma secretases, Notch ligands, or ADAM10.

4710-

CUR,

Curcumin inhibits migration and invasion of non-small cell lung cancer cells through up-regulation of miR-206 and suppression of PI3K/AKT/mTOR signaling pathway

in-vitro,

Lung,

A549

TumCMig↓, Curcumin significantly inhibited migration and invasion in A549 cells, accompanied by significantly elevated miR-206 expression.
TumCI↓,
miR-206↑, Overexpression of miR-206 could inhibit migration and invasion of A549 cells, but it could also significantly decrease the phosphorylation levels of mTOR and AKT.
p‑mTOR↓,
p‑Akt↓,

2821-

CUR,

Antioxidant curcumin induces oxidative stress to kill tumor cells (Review)

Review,

Var,

*antiOx↑, Curcumin is a plant polyphenol in turmeric root and a potent antioxidant
*NRF2↑, regulation by nuclear factor erythroid 2-related factor 2, thereby suppressing reactive oxygen species (ROS) and exerting anti-inflammatory, anti-infective and other pharmacological effects
*ROS↓,
*Inflam↓,
ROS↑, Of note, curcumin induces oxidative stress in tumors. curcumin-induced accumulation of ROS in tumors to kill tumor cells has been noted in several studies
p‑ERK↑, Curcumin promoted ERK/JNK phosphorylation, causing elevated ROS levels and triggering mitochondria-dependent apoptosis
ER Stress↑, Curcumin triggered disturbances in Ca2+ homeostasis, leading to endoplasmic reticulum stress, mitochondrial damage and apoptosis
mtDam↑,
Apoptosis↑,
Akt↓, Curcumin inhibited the AKT/mTOR/p70S6K signaling pathway
mTOR↓,
HO-1↑, Curcumin-induced HO-1 overexpression led to a disturbed intracellular iron distribution and triggered the Fenton reaction
Fenton↑,
GSH↓, Non-small cell lung cancer: Curcumin induced a decrease in GSH and an increase in ROS levels and iron accumulation
Iron↑,
p‑JNK↑, Curcumin causes mitochondrial damage by promoting phosphorylation of ERK and JNK, resulting in the increased release of ROS and cytochrome c into the cytoplasm, thereby triggering a mitochondrion-dependent pathway of apoptosis
Cyt‑c↑,
ATF6↑, thyroid cancer with curcumin, both activating transcription factor (ATF) 6 and the ER stress marker C/EBP homologous protein (CHOP) were activated by curcumin and Ca2+-ATPase activity was also affected.
CHOP↑,

2688-

CUR,

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

Review,

Var,

Review,

AD,

*ROS↓, CUR reduced the production of ROS
*SOD↑, CUR also upregulated the expression of superoxide dismutase (SOD) genes
p16↑, The effects of CUR on gene expression in cancer-associated fibroblasts obtained from breast cancer patients has been examined. CUR increased the expression of the p16INK4A and other tumor suppressor proteins
JAK2↓, CUR decreased the activity of the JAK2/STAT3 pathway
STAT3↓,
CXCL12↓, and many molecules involved in cellular growth and metastasis including: stromal cell-derived factor-1 (SDF-1), IL-6, MMP2, MMP9 and TGF-beta
IL6↓,
MMP2↓,
MMP9↓,
TGF-β↓,
α-SMA↓, These effects reduced the levels of alpha-smooth muscle actin (alpha-SMA) which was attributed to decreased migration and invasion of the cells.
LAMs↓, CUR suppressed Lamin B1 and
DNAdam↑, induced DNA damage-independent senescence in proliferating but not quiescent breast stromal fibroblasts in a p16INK4A-dependent manner.
*memory↑, CUR has recently been shown to suppress memory decline by suppressing beta-site amyloid precursor protein cleaving enzyme 1 (BACE1= Beta-secretase 1, an important gene in AD) expression which is implicated in beta-amyoid pathology in 5xFAD transgenic
*cognitive↑, CUR was found to decrease adiposity and improve cognitive function in a similar fashion as CR in 15-month-old mice.
*Inflam↓, The effects of CUR and CR were positively linked with anti-inflammatory or antioxidant actions
*antiOx↑,
*NO↑, CUR treatment increased nNOS expression, acidity and NO concentration
*MDA↓, CUR treatment resulted in decreased levels of MDA
*ROS↓, CUR treatment was determined to cause reduction of ROS in the AMD-RPEs and protected the cells from H2O2-induced cell death by reduction of ROS levels.
DNMT1↓, CUR has been shown to downregulate the expression of DNA methyl transferase I (DNMT1)
ROS↑, induction of ROS and caspase-3-mediated apoptosis
Casp3↑,
Apoptosis↑,
miR-21↓, CUR was determined to decrease both miR-21 and anti-apoptotic protein expression.
LC3II↓, CUR also induced proteins associated with cell death such as LC3-II and other proteins in U251 cells
ChemoSen↑, The combined CUR and temozolomide treatment resulted in enhanced toxicity in U-87 glioblastoma cells.
NF-kB↓, suppression of NF-kappaB activity
CSCs↓, Dendrosomal curcumin increased the expression of miR-145 and decreased the expression of stemness genes including: NANOG, OCT4A, OCT4B1, and SOX2 [113]
Nanog↓,
OCT4↓,
SOX2↓,
eff↑, A synergistic interaction was observed when emodin and CUR were combined in terms of inhibition of cell growth, survival and invasion.
Sp1/3/4↓, CUR inducing ROS which results in suppression of specificity protein expression (SP1, SP3 and SP4) as well as miR-27a.
miR-27a-3p↓,
ZBTB10↑, downregulation of miR-27a by CUR, increased expression of ZBTB10 occurred
SOX9?, This resulted in decreased SOX9 expression.
ChemoSen↑, CUR used in combination with cisplatin resulted in a synergistic cytotoxic effect, while the effects were additive or sub-additive in combination with doxorubicin
VEGF↓, Some of the effects of CUR treatment are inhibition of NF-κB activity and downstream effector proteins, including: VEGF, MMP-9, XIAP, BCL-2 and Cyclin-D1.
XIAP↓,
Bcl-2↓,
cycD1/CCND1↓,
BioAv↑, Piperine is an alkaloid found in the seeds of black pepper (Piper nigrum) and is known to enhance the bioavailability of several therapeutic agents, including CUR
Hif1a↓, CUR inhibits HIF-1 in certain HCC cell lines and in vivo studies with tumor xenografts. CUR also inhibited EMT by suppressing HIF-1alpha activity in HepG2 cells
EMT↓,
BioAv↓, CUR has a poor solubility in aqueous enviroment, and consequently it has a low bioavailability and therefore low concentrations at the target sites.
PTEN↑, CUR treatment has been shown to result in activation of PTEN, which is a target of miR-21.
VEGF↓, CUR treatment resulted in a decrease of VEGF and activated Akt.
Akt↑,
EZH2↓, CUR also suppressed EZH2 expression by induction of miR-let 7c and miR-101.
NOTCH1↓, The expression of NOTCH1 was inhibited upon EZH2 suppression [
TP53↑, CUR has been shown to activate the TP53/miR-192-5p/miR-215/XIAP pathway in NSCLC.
NQO1↑, CUR can also induce the demethylation of the nuclear factor erythroid-2 (NF-E2) related factor-2 (NRT2) gene which in turn activates (NQO1), heme oxygenase-1 (HO1) and an antioxidant stress pathway which can prevent growth in mouse TRAMP-C1 prostate
HO-1↑,

2654-

CUR,

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Review,

Var,

ROS↑, ROS induction has been implicated as one of the mechanisms of the anticancer activity of curcumin and its derivatives in various cancers
Catalase↓, Curcumin induces ROS by inhibiting the activity of various ROS-related metabolic enzymes, such as CAT, SOD1, glyoxalase 1, and NAD(P)H dehydrogenase [quinone] 1 [146,149]
SOD1↓,
GLO-I↓,
NADPH↓,
TumCCA↑, ROS accumulation further mediates G1 or G2/M cell cycle arrest [146,147,150,154], senescence [146], and apoptosis.
Apoptosis↑,
Akt↓, downregulation of AKT phosphorylation [145
ER Stress↑, endoplasmic reticulum stress (namely through the PERK–ATF4–CHOP axis)
JNK↑, activation of the JNK pathway [151],
STAT3↓, and inhibition of STAT3 [155].
BioAv↑, Additionally, the combination of curcumin and piperine, a pro-oxidative phytochemical that drastically increases the bioavailability of curcumin in humans

3576-

CUR,

Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer's Disease

Review,

AD,

*Inflam↓, known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions.
*antiOx↑,
*memory↑,
*Aβ↓, curcumin prevents Aβ aggregation and crosses the blood-brain barrier,
*BBB↑,
*cognitive↑, curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD
*tau↓, curcumin's effect on inhibition of A and tau,copper binding ability, cholesterol lowering ability, anti-inflammatory and modulation of microglia, acetylcholinesterase (AChE) inhibition, antioxidant properties,
*LDL↓,
*AChE↓,
*IL1β↓, Curcumin reduced the levels of oxidized proteins and IL1B in the brains of APP mice
*IronCh↑, Curcumin binds to redox-active metals, iron and copper
*neuroP↑, Curcumin, a neuroprotective agent, has poor brain bioavailability.
*BioAv↝,
*PI3K↑, They found that curcumin significantly upregulates phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor E2-related factor-2 (Nrf2), heme oxygenase 1, and ferritin expression
*Akt↑,
*NRF2↑,
*HO-1↑,
*Ferritin↑,
*HO-2↓, and that it significantly downregulates heme oxygenase 2, ROS, and A40/42 expression.
*ROS↓,
*Ach↑, significant increase in brain ACh, glutathione, paraoxenase, and BCL2 levels with respect to untreated group associated with significant decrease in brain AChE activity,
*GSH↑,
*Bcl-2↑,
*ChAT↑, nvestigation revealed that the selected treatments caused marked increase in ChAT positive cells.

2979-

CUR,

GB,

Curcumin overcome primary gefitinib resistance in non-small-cell lung cancer cells through inducing autophagy-related cell death

in-vitro,

Lung,

H157

in-vitro,

Lung,

H1299

EGFR↓, Combination treatment with curcumin and gefitinib markedly downregulated EGFR activity through suppressing Sp1 and blocking interaction of Sp1 and HADC1,
Sp1/3/4↓,
ERK↓, and markedly suppressed receptor tyrosine kinases as well as ERK/MEK and AKT/S6K pathways in the resistant NSCLC cells.
MEK↓,
Akt↓,
S6K↓,

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↑,

463-

CUR,

Curcumin induces autophagic cell death in human thyroid cancer cells

in-vitro,

Thyroid,

10, 12.5, 20, 25, 30, 40 and 50 µM, 24 and 72 h

in-vitro,

Thyroid,

FTC-133

in-vitro,

Thyroid,

BCPAP

in-vitro,

Thyroid,

8505C

TumAuto↑,
LC3II↑,
Beclin-1↑,
p‑p38↑,
p‑JNK↑,
p‑ERK↑, p-ERK1/2
p62↓,
p‑PDK1↓,
p‑Akt↓,
p‑p70S6↓,
p‑PIK3R1↓,
p‑S6↓,
p‑4E-BP1↓,

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

435-

CUR,

Antitumor activity of curcumin by modulation of apoptosis and autophagy in human lung cancer A549 cells through inhibiting PI3K/Akt/mTOR pathway

in-vitro,

Lung,

A549

5, 10, 20 and 40 μM, 24, 48, 72 and 96 h

Apoptosis↑,
TumAuto↑,
LC3‑Ⅱ/LC3‑Ⅰ↑,
Beclin-1↑,
p62↓,
PI3K↓,
Akt↓,
mTOR↓,
p‑Akt↓,
p‑mTOR↓,

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↓,

452-

CUR,

Curcumin downregulates the PI3K-AKT-mTOR pathway and inhibits growth and progression in head and neck cancer cells

vitro+vivo,

HNSCC,

SCC9

0, 25, 10, 5, 2.5, 1.25 and 0.75 μM, 24 and 48 h

41uM

vitro+vivo,

HNSCC,

FaDu

vitro+vivo,

HNSCC,

HaCaT

TumCCA↑, arrested cell cycle at phase G2 /M
PI3k/Akt/mTOR↓,
Casp3↑,
EGFR↓, 0.18 fold
EGF↑, Curcumin induced a noticeable increase in the expression of EGF (11.3-fold change)
PRKCG↑, 13.2 fold
p‑Akt↓,
p‑mTOR↓,
RPS6KA1↓, 0.17 fold
EIF4E↓, 0.18 fold
proCasp3↓,

1485-

CUR,

Chemo,

Rad,

Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs

Review,

Var,

ChemoSen↑, Such effects of curcumin were due to its ability to sensitize cancer cells for increased production of ROS
NF-kB↓, it downregulates various growth regulatory pathways and specific genetic targets including genes for NF-κB, STAT3, COX2, Akt
*STAT3↓, curcumin acts as a chemosensitizer and radiosensitizer has also been studied extensively. For example, it downregulates various growth regulatory pathways and specific genetic targets including genes for NF-kB, STAT3, COX2, Akt,
*COX2↓,
*Akt↓,
*NRF2↑, The protective effects of curcumin appear to be mediated through its ability to induce the activation of NRF2 and induce the expression of antioxidant enzymes (e.g., hemeoxygenase-1, glutathione peroxidase
*HO-1↑,
*GPx↑,
*NADPH↑,
*GSH↑, increase glutathione (a product of the modulatory subunit of gamma-glutamyl-cysteine ligase)
*ROS↓, dietary curcumin can inhibit chemotherapy-induced apoptosis via inhibition of ROS generation and blocking JNK signaling
*p300↓, inhibit p300 HAT activity
radioP↑, radioprotector for normal organs
chemoP↑, curcumin has also been shown to protect normal organs such as liver, kidney, oral mucosa, and heart from chemotherapy and radiotherapy-induced toxicity.
RadioS↑,

476-

CUR,

The effects of curcumin on proliferation, apoptosis, invasion, and NEDD4 expression in pancreatic cancer

in-vitro,

PC,

PATU-8988

5, 10, 15 and 20 μM, 48 and 72 h

in-vitro,

PC,

PANC1

TumCMig↓,
TumCI↓,
Apoptosis↑,
NEDD9↓,
p‑Akt↓,
p‑mTOR↓,
PTEN↑,
p73↑,
β-TRCP↑,

480-

CUR,

Curcumin exerts its tumor suppressive function via inhibition of NEDD4 oncoprotein in glioma cancer cells

in-vitro,

GBM,

SNB19

10, 15, 20 and 25 µM, 48 and 72 h

TumCP↓,
TumCMig↓,
Apoptosis↑,
TumCCA↑, G2/M phase
NEDD9↓,
NOTCH1↓,
p‑Akt↓,

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↓,

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↓,

12-

CUR,

Curcumin inhibits the Sonic Hedgehog signaling pathway and triggers apoptosis in medulloblastoma cells

in-vitro,

MB,

DAOY

 20 uM

HH↓, Curcumin inhibits the Sonic Hedgehog signaling pathway
Shh↓, curcumin inhibited the Shh-Gli1 signaling pathway by downregulating the Shh protein
Gli1↓,
PTCH1↓,
cMyc↓,
n-MYC↓,
cycD1/CCND1↓,
Bcl-2↓,
NF-kB↓,
Akt↓,
β-catenin/ZEB1↓, curcumin reduced the levels of beta-catenin
survivin↓,
Apoptosis↑, Consequently, apoptosis was triggered by curcumin through the mitochondrial pathway via downregulation of Bcl-2, a downstream anti-apoptotic effector of the Shh signaling.
ChemoSen↑, curcumin enhances the killing efficiency of nontoxic doses of cisplatin and gamma-rays.
RadioS↑,
eff↑, we present clear evidence that piperine, an enhancer of curcumin bioavailability in humans

15-

CUR,

UA,

Effects of curcumin and ursolic acid in prostate cancer: A systematic review

Review,

Pca,

NF-kB↝, involve NF-κB, Akt, androgen receptors, and apoptosis pathways.
Akt↝, see figure 5
AR↝,
Apoptosis↝,
Bcl-2↝,
Casp3↝,
BAX↝,
P21↝,
ROS↝,
Bcl-xL↝,
JNK↝,
MMP2↝,
P53↝,
PSA↝,
VEGF↝,
COX2↝,
cycD1/CCND1↝,
EGFR↝,
IL6↝,
β-catenin/ZEB1↝,
mTOR↝,
NRF2↝,
AP-1↝,
Cyt‑c↝,
PI3K↝,
PTEN↝,
Cyc↝,
TNF-α↝,

123-

CUR,

Synthesis of novel 4-Boc-piperidone chalcones and evaluation of their cytotoxic activity against highly-metastatic cancer cells

in-vitro,

Colon,

LoVo

 0.84–34.7 μg/mL

 curcumin analog

in-vitro,

Colon,

COLO205

 0.84–34.7 μg/mL

 curcumin analog

in-vitro,

Pca,

PC3

 17.1–22.9 μg/mL

 curcumin analog

in-vitro,

Pca,

22Rv1

 17.1–22.9 μg/mL

 curcumin analog

NF-kB↓, curcumin analog
ATF3↑, our study showed that ATF3 was up-regulated by curcumin in both LNCaP and C4-2B cells
HO-1↑, Our data confirmed the tumor-inhibitory effects of HMOX-1 gene in prostate cancer cells, which was up-regulated by curcumin treatment.
Wnt↓, Wnt, PIK3/AKT/mTOR, and NF-κB signaling pathways were primarily inhibited by curcumin treatment
Akt↓,
mTOR↓,
PTEN↑, and PTEN dependent cell cycle arrest and apoptosis pathways were found to be elevated.
Apoptosis↑,
TGF-β↓, TGF-β signaling pathway was inhibited by curcumin treatment in androgen-dependent and independent manners.
PPARγ↑, Curcumin was also shown to induce PPAR-γ gene expression and inhibit hepatic stellate cell (HSC) activation by interrupting TGF-β signaling in vitro

424-

CUR,

Curcumin inhibits autocrine growth hormone-mediated invasion and metastasis by targeting NF-κB signaling and polyamine metabolism in breast cancer cells

in-vitro,

BC,

MCF-7

5, 10, 15, 20, 25 and 30 µM, 24, 48 and 72 h

in-vitro,

BC,

MDA-MB-231

Src↓,
p‑STAT1↓, pSTAT-1
p‑Akt↓,
p‑p44↓, p-p44
p‑p42↓, p-p42
RAS↓,
Raf↓, c-RAF
Vim↓,
β-catenin/ZEB1↓,
P53↓,
Bcl-2↓,
Mcl-1↓,
PIAS-3↑,
SOCS-3↑,
SOCS1↑,
ROS↑,
NF-kB↓, NF-kB inactivation, ROS generation and PA depletion in MCF-7, MDA-MB-453 and MDA-MB-231 breast can- cer cells
PAO↑,
SSAT↑,
P21↑,
Bak↑,

425-

CUR,

Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells

in-vitro,

BC,

T47D

10 and 30 µM, 24 and 48 h

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MDA-MB-468

CDC25↓,
cDC2↓,
P21↑,
p‑Akt↓,
p‑mTOR↓, phosphorylation
Bcl-2↓,
BAX↑,
Casp3↑,

159-

CUR,

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

in-vitro,

Pca,

DU145

ROS↑, at higher concentrations
p‑Jun↑, phosphorylation
p‑p38↑, Moreover, increased p38 phosphorylation was decreased soon after 4 h of curcumin treatment
TumAuto↑, curcumin-induced autophagy was related to caspase-dependent apoptotic cell death,
Casp8↑, Necrotic cell death by autophagy-induced caspase 8/9 degradation lasts until late stages of cell death after curcumin treatmen
Casp9↑,
Akt↓, decreased activities of Akt, ERK, and p38 after curcumin treatment (
ERK↓,
p38↓,

165-

CUR,

Curcumin interrupts the interaction between the androgen receptor and Wnt/β-catenin signaling pathway in LNCaP prostate cancer cells

in-vitro,

Pca,

LNCaP

AR↓, Curcumin was shown to induce significant inhibition of AR expression in a dose-dependent manner
β-catenin/ZEB1↓, Curcumin repressed the nuclear accumulation of b-catenin
p‑Akt↓, In this study, we showed that curcumin suppressed phosphorylation of both Akt and GSK-3b.
GSK‐3β↓,
p‑β-catenin/ZEB1↑, phosphorylated
cycD1/CCND1↓, cyclin D1 and c-myc, the target gene of the β-catenin/T-cell factor transcriptional complex, were also decreased
cMyc↓,
chemoPv↑, Curcumin, a dietary yellow pigment of Curcuma longa, has emerged as having a chemopreventive role.
TumCP↓, Curcumin inhibited the proliferation of LNCaP prostate cancer cells

168-

CUR,

Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism

in-vitro,

Pca,

PC3

Akt↓, Curcumin-mediated inhibition of Akt/mTOR signaling is dependent on calyculin A-sensitive protein phosphatase activity
mTOR↓,
AMPK↑,
TAp63α↑, MAP kinases
TumCP↓, Curcumin inhibited DNA/protein synthesis, cell proliferation, and Akt/mTOR signaling in PC-3 cells

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↑,

4827-

QC,

CUR,

Synthetic Pathways and the Therapeutic Potential of Quercetin and Curcumin

Review,

Var,

*AntiCan↑, their anti-cancer effects, but also with regard to their anti-diabetic, anti-obesity, anti-inflammatory, and anti-bacterial actions.
*Inflam↓,
*Bacteria↓,
*AntiDiabetic↑,
*ROS↓, suppression of ROS formation via the inhibition of the enzyme activities involved in their production, or via scavenging ROS directly by acting as hydrogen donors; the chelation of the metal ions that induce ROS production;
*SOD↑, quercetin can eliminate free radicals and help maintain a stable redox state in cells by increasing anti-oxidant enzymes, such as superoxide dismutase (SOD), and catalase expressions, as well as the level of reduced glutathione (GSH)
*Catalase↑,
*GSH↑,
*NRF2↑, Quercetin can protect human granulosa cells from oxidative stress by inducing Nrf2 expression at both the gene and protein levels, which in turn induces the anti-oxidant thioredoxin (Trx) system.
*Trx↑,
*IronCh↑, pure curcumin, a metal chelator, directly removes ROS and regulates numerous enzymes.
*MDA↑, It has the potential to reduce the concentration of malondialdehyde (MDA) in serum and increase the total anti-oxidant potential
cycD1/CCND1↓, Cyclin D1 expression was significantly decreased in quercetin-treated ovarian SKOV-3 cells, but not in cisplatin (CDDP)-resistant SKOV3/CDDP cells.
PI3K↓, The levels of PI3K and phospho-Akt were decreased in curcumin-treated SKOV3 cells, which in turn increased caspase-3 and Bax levels.
Casp3↑,
BAX↑,
ChemoSen↑, Curcumin enhanced the efficacy of chemotherapy in colorectal cancer cells.
ROS↑, suggesting that quercetin-induced cytotoxicity and autophagy were initiated by the generation of ROS
eff↑, quercetin or curcumin with chemotherapeutic agents, as shown below, considerably enhances the antitumor potencies of doxorubicin (DOX) and cisplatin.
MMP↓, The synergistic treatment with curcumin and quercetin inhibited the cell proliferation associated with the loss of mitochondrial membrane potential (ΔΨm), the release of cytochrome c, a decrease in AKT and ERK phosphorylation in MGC803 human gastric
Cyt‑c↑,
Akt↓,
ERK↓,

139-

Tomatine,

CUR,

Combination of α-Tomatine and Curcumin Inhibits Growth and Induces Apoptosis in Human Prostate Cancer Cells

in-vitro,

Pca,

PC3

NF-kB↓, synergistic inhibition of NF-κB activity and a potent decrease in the expression of its downstream gene Bcl-2 in the cells.
Bcl-2↓,
p‑Akt↓, strong decreases in the levels of phospho-Akt and phosphor-ERK1/2 were found in PC-3 cells treated with α-tomatine and curcumin in combination
p‑ERK↓, ERK1/2
TumCG↓, α-tomatine in combination with curcumin may be an effective strategy for inhibiting the growth of prostate cancer.
Apoptosis↑, α-Tomatine and curcumin induce apoptosis in PC-3 cells
PCNA↓, Combined treatment with α-tomatine and curcumin had a more potent effect on decreasing the number of PCNA positive cells than either agent used alone
BioAv↓, However, the bioavailability of curcumin is low

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,

Sprague–Dawley rats. 50 mg/kg BW Tq + 100 mg/kg BW Cur, with or without cisplatin-treatment were administered for 5 days

*creat↓, BUN, creatinine, CK and pro-inflammatory cytokines like TNF-α, IL-6 and MRP-1 to be elevated in the cisplatin-treated group while reducing glomerular filtration rate. Tq + Cur treatment significantly improved these conditions.
*TNF-α↓,
*IL6↓,
*MRP↓,
*GFR↑,
*mt-ATPase↑, antioxidant enzyme levels and mitochondrial ATPases were restored upon treatment,
*p‑Akt↑, Tq + Cur treatment increased the expressions of phosphorylated Akt, Nrf2 and HO-1 proteins while decreasing the levels of cleaved caspase 3 and NFκB in kidney homogenates.
*NRF2↑,
*HO-1↑,
*Casp3↓,
*NF-kB↓,
*RenoP↑, In summary, Tq + Cur had protective effects on cisplatin-induced nephrotoxicity and renal injury

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 31

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes ⓘ

chemoP↑, 1, chemoPv↑, 1, radioP↑, 1,
Total Targets: 205

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 4, Catalase↑, 1, GPx↑, 1, GSH↑, 3, HO-1↑, 3, HO-2↓, 1, MDA↓, 1, MDA↑, 1, NRF2↑, 5, ROS↓, 6, SOD↑, 2, Trx↑, 1,

Metal & Cofactor Biology ⓘ

Ferritin↑, 1, IronCh↑, 2,

Core Metabolism/Glycolysis ⓘ

LDL↓, 1, NADPH↑, 1,

Cell Death ⓘ

Akt↓, 1, Akt↑, 1, p‑Akt↑, 1, Bcl-2↑, 1, Casp3↓, 1,

Transcription & Epigenetics ⓘ

Ach↑, 1,

Proliferation, Differentiation & Cell State ⓘ

p300↓, 1, PI3K↑, 1, STAT3↓, 1,

Migration ⓘ

mt-ATPase↑, 1,

Angiogenesis & Vasculature ⓘ

NO↑, 1,

Barriers & Transport ⓘ

BBB↑, 1, MRP↓, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, IL1β↓, 1, IL6↓, 1, Inflam↓, 5, NF-kB↓, 1, TNF-α↓, 1,

Synaptic & Neurotransmission ⓘ

AChE↓, 1, ChAT↑, 1, tau↓, 1,

Protein Aggregation ⓘ

Aβ↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,

Clinical Biomarkers ⓘ

creat↓, 1, Ferritin↑, 1, IL6↓, 1,

Functional Outcomes ⓘ

AntiCan↑, 1, AntiDiabetic↑, 1, cognitive↑, 2, GFR↑, 1, memory↑, 2, neuroP↑, 1, RenoP↑, 1,

Infection & Microbiome ⓘ

Bacteria↓, 1,
Total Targets: 51

Scientific Paper Hit Count for: Akt, PKB-Protein kinase B

31 Curcumin
1 gefitinib, erlotinib
1 Chemotherapy
1 Radiotherapy/Radiation
1 Photodynamic Therapy
1 Ursolic acid
1 nelfinavir/Viracept
1 Docetaxel
1 Quercetin
1 Tomatine
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#:4  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Database Query Results : Curcumin, , Akt

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 ⓘ

Synaptic & Neurotransmission ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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