Curcumin / Akt 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

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↑, *Inflam↓, PI3K↓, Akt↓, mTOR↓, Wnt↓, β-catenin/ZEB1↓, NF-kB↓, HH↓, NOTCH↓, JAK↓, STAT3↓, 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↓, TumCI↓, miR-206↑, p‑mTOR↓, p‑Akt↓,

2821-

CUR,

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

Review,

Var,

*antiOx↑, *NRF2↑, *ROS↓, *Inflam↓, ROS↑, p‑ERK↑, ER Stress↑, mtDam↑, Apoptosis↑, Akt↓, mTOR↓, HO-1↑, Fenton↑, GSH↓, Iron↑, p‑JNK↑, Cyt‑c↑, ATF6↑, CHOP↑,

2654-

CUR,

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Review,

Var,

ROS↑, Catalase↓, SOD1↓, GLO-I↓, NADPH↓, TumCCA↑, Apoptosis↑, Akt↓, ER Stress↑, JNK↑, STAT3↓, BioAv↑,

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↓, Sp1/3/4↓, ERK↓, 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↓, 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↑, 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‑Akt↓, Akt↓, cl‑Casp9↑, cl‑PARP↑,

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↑, 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↑, PI3k/Akt/mTOR↓, Casp3↑, EGFR↓, EGF↑, PRKCG↑, p‑Akt↓, p‑mTOR↓, RPS6KA1↓, EIF4E↓, 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↑, NF-kB↓, *STAT3↓, *COX2↓, *Akt↓, *NRF2↑, *HO-1↑, *GPx↑, *NADPH↑, *GSH↑, *ROS↓, *p300↓, radioP↑, chemoP↑, 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↑, 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↓, STAT3↓, p‑Akt↓, Mcl-1↓, Bcl-xL↓, cl‑PARP↑, miR-21↓, miR-205↑, TumCG↓, TumCP↓, 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↓, Shh↓, Gli1↓, PTCH1↓, cMyc↓, n-MYC↓, cycD1/CCND1↓, Bcl-2↓, NF-kB↓, Akt↓, β-catenin/ZEB1↓, survivin↓, Apoptosis↑, ChemoSen↑, RadioS↑, eff↑,

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↓, ATF3↑, HO-1↑, Wnt↓, Akt↓, mTOR↓, PTEN↑, Apoptosis↑, TGF-β↓, PPARγ↑,

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↓, p‑Akt↓, p‑p44↓, p‑p42↓, RAS↓, Raf↓, Vim↓, β-catenin/ZEB1↓, P53↓, Bcl-2↓, Mcl-1↓, PIAS-3↑, SOCS-3↑, SOCS1↑, ROS↑, NF-kB↓, 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↓, 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↑, p‑Jun↑, p‑p38↑, TumAuto↑, Casp8↑, Casp9↑, Akt↓, 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↓, β-catenin/ZEB1↓, p‑Akt↓, GSK‐3β↓, p‑β-catenin/ZEB1↑, cycD1/CCND1↓, cMyc↓, chemoPv↑, TumCP↓,

168-

CUR,

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

in-vitro,

Pca,

PC3

Akt↓, mTOR↓, AMPK↑, TAp63α↑, TumCP↓,

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↑, ER Stress↑, ATF4↑, CHOP↑, TRIB3↑, ChemoSen↑, Casp3↑, cl‑PARP↑, BID↑, XBP-1↑,

4827-

QC,

CUR,

Synthetic Pathways and the Therapeutic Potential of Quercetin and Curcumin

Review,

Var,

*AntiCan↑, *Inflam↓, *Bacteria↓, *AntiDiabetic↑, *ROS↓, *SOD↑, *Catalase↑, *GSH↑, *NRF2↑, *Trx↑, *IronCh↑, *MDA↑, cycD1/CCND1↓, PI3K↓, Casp3↑, BAX↑, ChemoSen↑, ROS↑, eff↑, MMP↓, 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↓, Bcl-2↓, p‑Akt↓, p‑ERK↓, TumCG↓, Apoptosis↑, PCNA↓, BioAv↓,

Showing Research Papers: 1 to 27 of 27

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 27

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes ⓘ

chemoP↑, 1, chemoPv↑, 1, radioP↑, 1,
Total Targets: 144

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

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

Metal & Cofactor Biology ⓘ

IronCh↑, 1,

Core Metabolism/Glycolysis ⓘ

NADPH↑, 1,

Cell Death ⓘ

Akt↓, 1,

Proliferation, Differentiation & Cell State ⓘ

p300↓, 1, STAT3↓, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, Inflam↓, 3,

Functional Outcomes ⓘ

AntiCan↑, 1, AntiDiabetic↑, 1,

Infection & Microbiome ⓘ

Bacteria↓, 1,
Total Targets: 20

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

27 Curcumin
1 gefitinib, erlotinib
1 Chemotherapy
1 Radiotherapy/Radiation
1 Photodynamic Therapy
1 nelfinavir/Viracept
1 Docetaxel
1 Quercetin
1 Tomatine

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#:1
  wNotes=0  sortOrder:rid,rpid

Curcumin / Akt Cancer Research Results

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 ⓘ

Proliferation, Differentiation & Cell State ⓘ

Immune & Inflammatory Signaling ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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