GSK‐3β Cancer Research Results

GSK‐3β, Glycogen synthase kinase (GSK)3β: Click to Expand ⟱

Source:

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GSK3β is a crucial member of the Wnt/β-catenin-, hedgehog (Hh)-, notch- and c-myc-mediated major pro-oncogenic pathways, while also being a negative regulator of epithelial–mesenchymal transition (EMT). Accumulating evidence defines GSK3β as a potential therapeutic target in cancer, thus encouraging the development of GSK3β inhibitors for cancer treatment.
Glycogen synthase kinase 3 beta (GSK-3β) is a serine/threonine kinase that plays a crucial role in various cellular processes, including cell proliferation, differentiation, and apoptosis. Its expression and activity have been implicated in several types of cancer, often with varying prognostic implications.

In many cancers, decreased GSK-3β activity is associated with poor prognosis, while in others, increased activity may correlate with aggressive disease.

Scientific Papers found: Click to Expand⟱

6462-

1,8-Cin,

Modes of Action of 1,8-Cineol in Infections and Inflammation

Review,

Var,

Review,

AD,

*BioAv↑, become increasingly clear in the recent years that 1,8-Cineol spreads almost everywhere in the human body after its oral administration, from the gut to the blood to the brain.
*BBB↑,
*AntiViral↑, anti-viral effects have been observed to include numerous bacteria and fungi species.
*Bacteria↓,
*AntiFungal↑,
*Inflam↓, central mode of action of 1,8-Cineol is the inhibition of pro-inflammatory cytokine expression
*BioAv↑, 1,8-Cineol was detectable in nasal tissue samples after its oral administration for 14 days, which indicates the systemic distribution of 1,8-Cineol via the gut and the blood stream
*MUC2↓, significantly reduced expression levels of the mucin genes MUC2 and MUC19 in close association with a significantly attenuated activity of transcription factor NF-κB
*MUC19↓,
*NF-kB↓, reduced the expression levels of transcriptional activator nuclear factor (NF)-kB p65 and expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in lung tissues
*ICAM-1↓,
*VCAM-1↓,
DNAdam↑, colon cancer cells on the potential genotoxicity of 1,8-Cineol revealed a concentration-dependent increase in oxidative DNA damage, whereas it did not affect the cell viability due to DNA repair mechanisms
*lipid-P↓, suppressing the expression of lipid mediators and prostaglandin D2
*PGE2↓,
*IL4↓, decreased expression levels of different inflammatory cytokines such as interleukin (IL)-4, IL-6 and granulocyte macrophage colony stimulating factor (GM-CSF) in bronchial epithelial cells
*IL6↓,
*IL1β↓, 1,8-Cineol-containing leaf extracts significantly suppressed the expression of pro-inflammatory cytokines IL-1β and IL-6 [
*IL6↓,
eff↑, 1,8-Cineol in combination with ellagic acid has been shown to downregulate different cytokines such as transforming growth factor beta-1 (TGF-β1), Fascin-1 (FSCN1), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in p
TGF-β↓,
fascin↓,
VEGF↓,
MMP9↓,
*MAPK↓, 1,8-Cineol was shown to suppress the activation of the MAPK/ERK
*ERK↓,
JNK↓, decreased activities of transcription factor NFκB and the JNK (c-Jun N-terminal kinase)/AP-1 (activator protein-1) pathway in the human cancer cell lines U373 and HeLa in response to 1,8-Cineol, the active ingredient of the drug Soledum
Wnt↓, 1,8-Cineol acts as an inhibitor of the Wnt/β-catenin pathway in head and neck squamous cell carcinoma (HNSCC).
β-catenin/ZEB1↓,
GSK‐3β↑, decreased inhibition of glycogen synthase kinase 3 (GSK-3) and reduced levels of WNT11
*neuroP↑, 1,8-Cineol has been shown to have neuroprotective activity.
*GSK‐3β↓, decreased activity of GSK-3 in response to 1,8-Cineol could ameliorate advanced glycation end products,
*AGEs↓,
*BBB↑, eucalyptol reveals an opening effect on the blood–brain barrier
*NLRP3↓, controls inflammation by suppressing the NOD-like receptor pyrin domain-containing 3 (NLRP3) activation

4804-

ASTX,

Astaxanthin in cancer therapy and prevention (Review)

Review,

Var,

Review,

AD,

*antiOx↑, gained significant attention for its potent antioxidant, anti-inflammatory and anti-proliferative properties.
*Inflam↓,
ChemoSen⇅, In some instances, it reduces the cytotoxicity of cisplatin, particularly with cisplatin on the SKBR3 breast cancer cell line, indicating a potential protective effect. In certain cases, AXT enhances the cytotoxic effect of the chemotherapy drugs
chemoP↑, The present review detailed both in vitro and in vivo studies highlighting the effectiveness of AXT in sensitizing cancer cells to chemotherapy, thereby enhancing therapeutic outcomes and potentially reducing treatment-related side effects.
BioAv↑, incorporation of AXT in nanoparticle-based delivery systems has further improved its bioavailability
TumCP↑, AXT exhibits hormetic effects on U251-MG, T98G and CRT-MG cell lines, where low doses stimulate cell proliferation
ROS⇅, while higher doses induce apoptosis by triggering a dose-dependent oxidative stress response, significantly increasing reactive oxygen species (ROS) levels and promoting apoptosis
Apoptosis↑,
PI3K↑, AXT activates the PI3K/Akt/GSK3β pathway, leading to the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor, in SH-SY5Y cells under oxygen and glucose deprivation conditions
Akt↑,
GSK‐3β↑,
NRF2↑,
AntiCan↑, antioxidant, AXT has the potential to act as both an anticancer drug and a neuroprotectant.
*neuroP↑, AXT protects against oxidative stress, which causes mitochondrial dysfunction and apoptosis, thereby reducing the detrimental effects associated with neurodegenerative diseases such as Alzheimer's, Parkinson's
eff↑, The synergistic cytotoxic effect of AXT with melatonin showed enhanced efficacy in the T47D cell line compared with the MDA-MB-231 line
AntiTum↑, AXT effectively reduced tumor size and the number of cancer cells in mice, supporting its potential anti-tumor activity.

4305-

Ba,

Study on the Molecular Mechanism of Baicalin Phosphorylation of Tau Protein Content in a Cell Model of Intervention Cognitive Impairment

in-vitro,

NA,

SH-SY5Y

15μmol/L

*cognitive↑, In cell experiments, baicalein presented a positive impact on mild cognitive impairment by elevating P-AKT1 and P-GSK-3β levels while reducing the overall amount of P-tau.
*p‑Akt↑,
*p‑GSK‐3β↑,
*p‑tau↓,
*neuroP↑, baicalein demonstrates a neuroprotective by modulating pathways such as the NF-κB/MAPK signaling pathway and the AMPK/Nrf2 pathway.
*NF-kB↓,
*AMPK↑,
*NRF2↑,

5692-

BJ,

Seed oil of Brucea javanica induces apoptosis through the PI3K/Akt signaling pathway in acute lymphocytic leukemia Jurkat cells

vitro+vivo,

AML,

Apoptosis↑, BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction
Akt↓, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis
P53↑,
FOXO1↑,
GSK‐3β↑, The activation of GSK3β was also involved.
TumVol↓, In a 96-case clinical trial, BJOE treatment reduced tumor size and improved the quality of life for patients with gastrointestinal cancer and cervical cancer [18].
QoL↑,
BBB↑, As shown in pharmacokinetic studies, BJOE crossed the blood-brain barrier
OS↑, In another 100-case clinical trial, BJOE prolonged the survival of patients with brain meta- stases from lung cancer [24].
Dose↝, Currently, BJOE is intravenously administered for the clinical treatment of lung cancer [25-28] and gastric cancer [29-31]
MMP↓, MMP collapse and ROS production in Jurkat cells were also observed following BJOE treatment.
ROS↑,
XIAP↑, we found that BJOE targeted Akt to stimulate FoxO1 and XIAP to induce apoptosis.
Casp9↑, BJOE promoted the activation of caspase- 9, caspase-8 and caspase-3.
Casp8↑,
Casp3↑,
cl‑PARP↑, The cleavage of PARP proteins was also observed.
TumCCA↑, the sub-G1 phase cell percentages increased in all five samples in a BJOE concentration-dependent manner.

5768-

CAPE,

Neuroprotective Potential of Caffeic Acid Phenethyl Ester (CAPE) in CNS Disorders: Mechanistic and Therapeutic Insights

Review,

AD,

Review,

Park,

Review,

Stroke,

*antiOx↑, it possesses antioxidant, anti-inflammatory, antimitogenic, and anti-cancer activities, as shown by preclinical studies.
*Inflam↑,
*AntiCan↑,
*NRF2↑, figure 1
*GSK‐3β↑,
*Akt↑,
*PI3K↑, directly activates the PI3/Akt signaling pathway as well as leads to increased phosphorylation of GSK-3β to yield it inactive
*ROS↓, decrease in the reactive oxygen species levels (ROS)
*SOD↑,
*GSH↑,
*MDA↓,
*tau↓, reduced hyperphosphorylation of Tau protein
*neuroP↑, Accorded neuroprotection through increased PI3K activity and eNOS mediated nitric oxide synthesis
*memory↑, CAPE treatment in the doses of 6 mg/kg for 28 days led to an improvement in spatial memory and reduction in the malondialdehyde (MDA),
*AChE↓, Other mechanisms which may contribute to its beneficial effect include the inhibition of acetylcholinesterase activity, which has also been reported by several authors
*other↝, Different studies have demonstrated the effectiveness of CAPE in stroke models through its anti-inflammatory and antioxidant properties.
*lipid-P↓, decreasing membrane fluidity, lipid peroxidation, release of cardiolipin, and Cyt c

5886-

CAR,

Inhibition of TRPM7 with carvacrol suppresses glioblastoma functions in vivo

in-vivo,

GBM,

U87MG

flank xenograft GBM mouse model

in-vivo,

GBM,

U251

TRPM7↓, TRPM7 inhibitor, carvacrol
TumVol↓, carvacrol significantly reduced the tumour size in both mice injected with U87 and U251 cells, decreased p-Akt protein level and increased p-GSK3β protein levels
p‑Akt↓,
p‑GSK‐3β↑,
Dose↝, The carvacrol group received intraperitoneal injections (20, 40, or 60 mg/kg/day) for 5 days.

1145-

CHr,

Chrysin inhibits propagation of HeLa cells by attenuating cell survival and inducing apoptotic pathways

in-vitro,

Cerv,

HeLa

tumCV↓,
BAX↑,
BID↑,
BOK↑,
APAF1↑,
TNF-α↑,
FasL↑,
Fas↑,
FADD↑,
Casp3↑,
Casp7↑,
Casp8↑,
Casp9↑,
Mcl-1↓,
NAIP↓,
Bcl-2↓,
CDK4↓,
CycB/CCNB1↓,
cycD1/CCND1↓,
cycE1↓,
TRAIL↑,
p‑Akt↓,
Akt↓,
mTOR↓,
PDK1↓,
BAD↓,
GSK‐3β↑,
AMPK↑, AMPKa
p27↑,
P53↑,

3888-

Cin,

Cinnamon, a promising prospect towards Alzheimer's disease

NA,

AD,

*tau↓, mild-to-moderate AD through the inhibition of tau protein aggregation and prevention of the formation and accumulation of amyloid-β peptides
*Aβ↓,
*neuroP↑, cinnamon possesses neuroprotective effects interfering multiple oxidative stress and pro-inflammatory pathways.
*ROS↓,
*Inflam↓,
*cardioP↑, figure 1
*antiOx↑,
*cognitive↑,
*BBB↑, cinnamon compounds may either cross the blood brain barrier (BBB) or probably pass through other peripheral routes
*p‑GSK‐3β↑, Cinnamon increased phosphorylated GSK3 (critical for choline metabolism), inhibited AChE activity and increased neuron number in hippocampus area of these animals
*AChE↓, In sum, cinnamon spp. and its biologically active compounds target every 3 AD hallmarks; inhibition of AChE activity, abeta formation/aggregation and tau phosphorylation

6217-

CUR,

Curcumin: a therapeutic strategy in cancers by inhibiting the canonical WNT/β-catenin pathway

Review,

Var,

Wnt↓, Curcumin administration participates to the downregulation of the WNT/β-catenin pathway and thus, through this action, in tumor growth control.
β-catenin/ZEB1↓,
PPARγ↑, Curcumin stimulates PPARγ
Akt↓, Curcumin inhibits Akt pathway
*ROS↓, (1) Curcumin reduces oxidative
*Inflam↓, (2) Curcumin reduces chronic inflammation
Bcl-2↓, (4) Curcumin downregulates WNT pathway and its target genes, inhibits Bcl-2 and activates GSK-3beta;
GSK‐3β↑,
NF-kB↓, (5) Curcumin inhibits NF-ϰB and COX-2
COX2↓,

6675-

Deg,

Deguelin inhibits growth of breast cancer cells by modulating the expression of key members of the Wnt signaling pathway

in-vitro,

BC,

MCF7

in-vitro,

BC,

BT474

in-vitro,

BC,

T47D

in-vitro,

BC,

MDA-MB-231

TumCG↓, Deguelin at 1 mumol/L was found to inhibit the growth of the breast cancer cell lines tested with a range of 37% to 87%.
TumCCA↑, An arrest at the S phase of the cell cycle and apoptosis were shown in the MDA-MB-231 cells treated with deguelin.
Apoptosis↑, In addition to cell cycle arrest, the overall cell growth inhibition induced by deguelin could be due to increased apoptosis.
Wnt↓, Cumulatively, the data suggest that deguelin acts as an inhibitor of the Wnt/β-catenin signaling pathway, in part through activation of GSK-3β.
β-catenin/ZEB1↓,
GSK‐3β↑,
TNF-α↓, deguelin inhibits the mRNA expression of tumor necrosis factor-α, one of the most potent activators of the NF-κB pathway.
PI3K↓, deguelin reduced the gene expression of phosphatidylinositol 3-kinase (PI3K), MAP3K8, PKAc, and CK2 as such treatment with deguelin blocked the PI3K–Akt–NF-κB signaling cascade.
Akt↓,

1860-

dietFMD,

Chemo,

Fasting-mimicking diet blocks triple-negative breast cancer and cancer stem cell escape

in-vitro,

BC,

SUM159

in-vitro,

BC,

4T1

PI3K↑, FMD activates PI3K-AKT, mTOR, and CDK4/6 as survival/growth pathways, which can be targeted by drugs to promote tumor regression.
Akt↑,
mTOR↑,
CDK4↑,
CDK6↑,
hyperG↓, FMD cycles also prevent hyperglycemia and other toxicities caused by these drugs.
TumCG↓, cycles of FMD significantly slowed down tumor growth, reduced tumor size, and caused an increased expression of intratumor Caspase3
TumVol↓,
Casp3↑,
BG↓, confirming our hypothesis that lowering intracellular glucose levels (through reduced extracellular levels or reduced uptake) reduces CSC survival
eff↑, 2DG potentiated the effect of FMD both in terms of delaying tumor progression and in decreasing the number of mammospheres derived by tumor masses,
eff∅, metformin did not show any additive or synergistic antitumor effect when combined with the FMD, thus suggesting that FMD and metformin have redundant effects on blood glucose levels
PKA↓, We have previously shown that prolonged fasting reduces the activity of protein kinase A (PKA) in different types of normal cells
KLF5↓, PKA inhibition resulted in the downregulation of KLF5, a potential therapeutic target for TNBC
p‑GSK‐3β↑, (GSK3β) phosphorylation
Nanog↓, stemness-associated genes NANOG and OCT4, and KLF2 and TBX3,
OCT4↓,
KLF2↓,
eff↑, Combining FMD cycles with PI3K/AKT/mTOR inhibitors results in long-term animal survival and reduces treatment-induced side effects
ROS↑, FMD resulted in an increased expression of pro-apoptotic molecules, such as BIM, and ASK1, a critical cellular stress sensor frequently activated by ROS, whose production was previously shown to be increased by the FMD
BIM↑,
ASK1↑,
PI3K↑, FMD cycles upregulate PI3K-AKT and mTOR pathways and downregulate CCNB-CDK1 while upregulating CCND-CDK4/6 signaling axes
Akt↑,
mTOR↑,
CDK1↓,
CDK4↑,
CDK6↑,
eff↑, combining STS with pictilisib, ipatasertib, and rapamycin, selective inhibitors for PI3K, AKT, and mTOR, respectively, resulted in enhanced cancer cell death and reduction of mammosphere numbers in SUM159 cells

4682-

EGCG,

Human cancer stem cells are a target for cancer prevention using (−)-epigallocatechin gallate

Review,

Var,

CSCs↓, EGCG inhibits the transcription and translation of genes encoding stemness markers, indicating that EGCG generally inhibits the self-renewal of CSCs.
EMT↓, EGCG inhibits the expression of the epithelial-mesenchymal transition phenotypes of human CSCs.
ChemoSen↑, Green tea prevents human cancer, and the combination of EGCG and anticancer drugs confers cancer treatment with tissue-agnostic efficacy.
CD133↓, CD133, CD44, ALDH1A1, Nanog, Oct4
CD44↓,
ALDH1A1↓,
Nanog↓,
OCT4↓,
TumCP↓, These results show that EGCG inhibits proliferation and induces apoptosis of lung CSCs
Apoptosis↑,
p‑GSK‐3β↓, EGCG (0–100 μM) inhibited the phosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser 9, which significantly increases the expression of GSK3β, and decreases the expression of β-catenin and its downstream target gene c-Myc.
GSK‐3β↑,
β-catenin/ZEB1↓,
cMyc↓,
XIAP↓, EGCG (30–60 μM) inhibits the expression of X-linked inhibitor of apoptosis protein (XIAP), Bcl2, and survivin as well as that of the EMT markers vimentin, Slug, Snail, and nuclear β-catenin.
Bcl-2↓,
survivin↓,
Vim↓,
Slug↓,
Snail↓,

2844-

FIS,

Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma (U-2 OS) cells

in-vitro,

OS,

U2OS

tumCV↓, Fisetin at 20-100 µM effectively reduced the viability of OS cells, and induced apoptosis by signifi-cantly inducing the expression of Caspases- 3,-8 and -9 and pro-apoptotic proteins (Bax and Bad) with subsequent down-regulation of Bcl-xL and Bcl-2
Apoptosis↑,
Casp3↑,
Casp8↑,
Casp9↑,
BAX↑,
BAD↑,
Bcl-2↓,
Bcl-xL↓,
PI3K↓, inhibited PI3K/Akt pathway and ERK1/2,
Akt↓,
ERK↓,
p‑JNK↑, it caused enhanced expressions of p-JNK, p-c-Jun and p-p38
p‑cJun↑,
p‑p38↑,
ROS↑, Fisetin-induced ROS generation and decrease in mitochondrial membrane potential
MMP↓, noticeable decline of mitochondrial transmembrane potential (ΔΨm) in a dose-dependent manner
mTORC1↓, fisetin at various concentrations (20-100 μM) caused a significant (p<0.05) decrease in the level of p-Akt and mTORC1 (an important effector protein of Akt), while up-regulated PTEN.
PTEN↑,
p‑GSK‐3β↓, Level of phosphorylated glycogensynthase kinase 3ǃ (GSK3ǃ), (a serine/threonine kinase) and cyclin D1 were potentially decreased by fisetin which is in line with raised non-phosphorylated levels of GSK3ǃ
GSK‐3β↑,
NF-kB↓, Down-regualtion of NF-κB along with significant up-regulations in IκB upon fisetin treatment correlates with the down-regulation of p-Akt levels.
IKKα↑,
Cyt‑c↑, activates the efflux of cytochrome C

2827-

FIS,

The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment

Review,

Var,

*antiOx↑, effective antioxidant, anti-inflammatory
*Inflam↓,
neuroP↑, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential.
hepatoP↑,
RenoP↑,
cycD1/CCND1↓, Figure 3
TumCCA↑,
MMPs↓,
VEGF↓,
MAPK↓,
NF-kB↓,
angioG↓,
Beclin-1↑,
LC3s↑,
ATG5↑,
Bcl-2↓,
BAX↑,
Casp↑,
TNF-α↓,
Half-Life↓, Fisetin was given at an effective dosage of 223 mg/kilogram intraperitoneally in mice. The plasma concentration declined biophysically, with a rapid half-life of 0.09 h and a terminal half-life of 3.1 h,
MMP↓, Fisetin powerfully improved apoptotic cells and caused the depolarization of the mitochondrial membrane.
mt-ROS↑, Fisetin played a role in the induction of apoptosis, independently of p53, and increased mitochondrial ROS generation.
cl‑PARP↑, fisetin-induced sub-G1 population as well as PARP cleavage.
CDK2↓, Moreover, the activities of cyclin-dependent kinases (CDK) 2 as well as CDK4 were decreased by fisetin and also inhibited CDK4 activity in a cell-free system, demonstrating that it might directly inhibit the activity of CDK4
CDK4↓,
Cyt‑c↑, Moreover, release of cytochrome c and Smac/Diablo was induced by fisetin
Diablo↑,
DR5↑, Fisetin caused an increase in the protein levels of cleaved caspase-8, DR5, Fas ligand, and TNF-related apoptosis-inducing ligand
Fas↑,
PCNA↓, Fisetin decreased proliferation-related proteins such as PCNA, Ki67 and phosphorylated histone H3 (p-H3) and decreased the expression of cell growth
Ki-67↓,
p‑H3↓,
chemoP↑, Paclitaxel treatment only showed more toxicity to normal cells than the combination of flavonoids with paclitaxel, suggesting that fisetin might bring some safety against paclitaxel-facilitated cytotoxicity.
Ca+2↑, Fisetin encouraged apoptotic cell death via increased ROS and Ca2+, while it increased caspase-8, -9 and -3 activities and reduced the mitochondrial membrane potential in HSC3 cells.
Dose↝, After fisetin treatment at 40 µM, invasion was reduced by 87.2% and 92.4%, whereas after fisetin treatment at 20 µM, invasion was decreased by 52.4% and 59.4% in SiHa and CaSki cells, respectively
CDC25↓, This study proposes that fisetin caused the arrest of the G2/M cell cycle via deactivating Cdc25c as well Cdc2 via the activation of Chk1, 2 and ATM
CDC2↓,
CHK1↑,
Chk2↑,
ATM↑,
PCK1↓, fisetin decreases the levels of SOS-1, pEGFR, GRB2, PKC, Ras, p-p-38, p-ERK1/2, p-JNK, VEGF, FAK, PI3K, RhoA, p-AKT, uPA, NF-ĸB, MMP-7,-9 and -13, whereas it increases GSK3β as well as E-cadherin in U-2 OS
RAS↓,
p‑p38↓,
Rho↓,
uPA↓,
MMP7↓,
MMP13↓,
GSK‐3β↑,
E-cadherin↑,
survivin↓, whereas those of survivin and BCL-2 were reduced in T98G cells
VEGFR2↓, Fisetin inhibited the VEGFR expression in Y79 cells as well as the angiogenesis of a tumor.
IAP2↓, The downregulation of cIAP-2 by fisetin
STAT3↓, fisetin induced apoptosis in TPC-1 cells via the initiation of oxidative damage and enhanced caspases expression by downregulating STAT3 and JAK 1 signaling
JAK1↓,
mTORC1↓, Fisetin acts as a dual inhibitor of mTORC1/2 signaling,
mTORC2↓,
NRF2↑, Moreover, In JC cells, the Nrf2 expression was gradually increased by fisetin from 8 h to 24 h

1121-

JG,

Juglone suppresses epithelial-mesenchymal transition in prostate cancer cells via the protein kinase B/glycogen synthase kinase-3β/Snail signaling pathway

in-vitro,

Pca,

LNCaP

E-cadherin↑,
N-cadherin↓,
Vim↓,
Snail↓,
GSK‐3β↑, prevented inactivation

496-

MF,

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

in-vitro,

BC,

MCF7

1mT, 200Hz, 24h

200 Hz reached the optimum inhibition effect

in-vitro,

BC,

ZR-75-1

in-vitro,

BC,

T47D

in-vitro,

BC,

MDA-MB-231

ROS↑, LF-MFs Enhanced the ROS Levels in MCF-7 and ZR75-1 Cells
PI3K↓, and inhibited the activities of the PI3K/AKT signaling pathways in MCF-7 and ZR-75-1 cells
Akt↓,
GSK‐3β↑, LF-MF Induced MCF-7 and ZR75-1 Cells Apoptosis by Activating GSK-3β
Apoptosis↑, LF-MF Induced Breast Cancer Cell Apoptosis
cl‑PARP↑, cleaved PARP-1
cl‑Casp3↑,
BAX↑,
Bcl-2↓,
CycB/CCNB1↓, Cyclin B1
TumCCA↑, failure of the transition from the G2 phase to M phase
p‑Akt↓,
TumCP↓, LF-MF Inhibited the Proliferation of Breast Cancer Cells
selectivity↑, The viabilities of HUVECs did not markedly reduce after exposure in LF-MF at the four selected frequencies for 6, 12, 24 or 36 h
eff↓, attenuated by ROS scavenger NAC

520-

MF,

Exposure to a 50-Hz magnetic field induced mitochondrial permeability transition through the ROS/GSK-3β signaling pathway

in-vitro,

Nor,

50 Hz, 0.4 mT, 60mins

Human amniotic epithelial cells

*MPT↑, MPT induced by MF exposure was mediated through the ROS/GSK-3β signaling pathway.
*Cyt‑c↑, induced Cyt-c release
*ROS↑, cells exposed to the MF showed increased intracellular reactive oxidative species (ROS) levels and glycogen synthase kinase-3β (GSK-3β) dephosphorylation at 9 serine residue (Ser(9))
*p‑GSK‐3β↑,
*eff↓, attenuated by ROS scavenger (N-acetyl-L-cysteine, NAC) or GSK-3β inhibitor
*MMP∅, no significant effect on mitochondrial membrane potential (ΔΨm)
*BAX↓, Bax declined around 15% which was statistically significant while the total level of Bcl-2 reminded unchanged in cells
*Bcl-2∅,

6490-

Nimb,

Nimbolide, a neem limonoid inhibits cytoprotective autophagy to activate apoptosis via modulation of the PI3K/Akt/GSK-3β signalling pathway in oral cancer

in-vitro,

Oral,

SCC4

6 and 6.2 µM

PI3K↓, Nimbolide negatively regulates PI3K/Akt signalling with consequent increase in p-GSK-3βTyr216, the active form of GSK-3β that inhibits autophagy.
Akt↓,
GSK‐3β↑, Nimbolide stimulates GSK-3β expression by modulating miR-126 and HOTAIR
MMP↓, Treatment of cells with nimbolide induced a change in fluorescence from red to green indicating collapse of the MMP
Apoptosis↑, Apoptosis induction in SCC131 and SCC4 cells upon nimbolide treatment was further confirmed by an increase in the Bax/Bcl-2 ratio and higher cytosolic cytochrome c relative to the mitochondrial fraction associated with increased expression of cleaved
Bax:Bcl2↑,
Cyt‑c↑,
cl‑Casp3↑, increased expression of cleaved caspase -9 and -3
cl‑Casp9↑,
TumAuto↑, Nimbolide induces autophagy in oral cancer cells
Beclin-1↓, 24 h of treatment with nimbolide Beclin-1 expression was decreased with increased expression of p62 associated with presence of truncated ATG5
p62↑,
PI3K↓, Nimbolide induces autophagy via inhibition of PI3K pathway in oral cancer cells
chemoPv↑, The chemopreventive efficacy of nimbolide is well established in the HBP model

6487-

Nimb,

Anticancer properties of nimbolide and pharmacokinetic considerations to accelerate its development

Review,

Var,

1-5uM

TumCP↓, anti-proliferation, induction of apoptosis, inhibition of metastasis and angiogenesis, and modulation of carcinogen-metabolizing enzymes.
Apoptosis↓,
TumMeta↑,
angioG↓,
*antiOx↑, nimbolidehas been found to possess antioxidant effect and free radical scavenging activities.
*eff↑, In comparison to azadirachtin and ascorbic acid (vitamin C), nimbolide was shown to be a more potent antioxidant
Apoptosis↑, Nimbolide induces apoptosis through diverse molecular mechanism(s).
MOMP↑, Nimbolide disrupts MOMP, which promotes caspases activation leading to apoptosis.
CDK1↓, Nimbolide also reduces the level of CDKs and cyclins, causing cell cycle arrest.
TumCCA↑,
MAPK↓, Nimbolide also abrogates various signaling cascades including MAPK (ERK1/2), JAK2/STAT3 and PI3K/Akt, leading to suppression of proliferation of a wide variety of human cancer cells.
JAK2↓,
STAT3↓,
PI3K↓,
Akt↓,
TumCP↓,
*NRF2↑, Nimbolide disrupts the Nrf2-KEAP1 complex and promotes the release of Nrf2, thus increasing levels of antioxidant and detoxification enzymes.
NF-kB↓, Inhibition of the NF-κB pathway also reduces the dissociation of GSK-3β from β-catenin, hence restraining the Wnt/β-catenin
GSK‐3β↑,
Wnt↓,
β-catenin/ZEB1↓,
chemoPv↑, nimbolide showed remarkable chemopreventive property.
Bcl-xL↓, Nimbolide treatmentdecreased the expression of antiapoptotic proteins(Bcl-xL, Bcl-2, survivin, caspase inhibitor molecules) and increased the expression of proapoptotic proteins (cytochrome c, Bax, Bad, Bid, cleaved caspases) in prostate cancer cells
Bcl-2↓,
survivin↓,
Cyt‑c↑,
BAX↑,
BID↑,
cl‑Casp↑,
P53↑, nimbolide acted by up-regulation of p53 levelin HeLa cells, thereby priming these cells towards apoptosis by destabilizing the mitochondria
DR5↑, Nimbolide up-regulated the expression of both DR5 and DR4 in chronic myeloid leukemia (KBM-5), multiple myeloma (U266), embryonic kidney carcinoma (A293), pancreatic adenocarcinoma (AsPC-1), and breast adenocarcinoma (MDA-MB-231) cells
DR4↑,
ROS↑, nimbolide resulted in generation of reactive oxygen species (ROS)
lipid-P↑, ROS also induced lipid peroxidation of cellular membranes, generating toxic metabolites such as malondialdehyde (MDA) that can react with DNA to form adducts to induce apoptosis.
MDA↑,
MMP2↓, nimbolide reduced mRNA expression of MMP-2, MMP-9, uPA and uPA receptor in breast cancer cells (MCF-7)
MMP9↓,
uPA↓,
ICAM-1↓, nimbolide was shown to downregulate the expression of MMP-9, ICAM-1, and CXCR4 in colorectal cancer xenografts
CXCR4↓,
CXCR2↓, nimbolide also reduced expression of CXCL8 and CXCR2 in breast cancers, and thus abrogated angiogenesis
angioG↓,
BBB↑, nimbolide might be able to cross blood-brain barrier (BBB) and the concentration could be sufficient for nimbolide to suppress intracranial tumour cell proliferation.

3099-

RES,

Resveratrol and cognitive decline: a clinician perspective

Review,

Nor,

NA,

AD,

*antiOx↑, In preclinical models of cognitive decline, resveratrol displays potent antioxidant activity by scavenging free radicals, reducing quinone reductase 2 activity and upregulating endogenous enzymes.
*ROS↓,
*cognitive↑,
*neuroP↑,
*SIRT1↑, By inducing SIRT1, resveratrol may promote neurite outgrowth and enhance neural plasticity in the hippocampal region
*AMPK↑, Resveratrol also induces neurogenesis and mitochondrial biogenesis by enhancing AMP-activated protein kinase (AMPK), which is known to stimulate neuronal differentiation and mitochondrial biogenesis in neurons.
*GPx↑, figure 1
*HO-1↑,
*GSK‐3β↑,
*COX2↓,
*PGE2↓, Resveratrol also inhibits pro-inflammatory enzyme (i.e., COX-1 and -2) expression, reduces NF-κB activation as well as PGE2, NO, and TNF-α production, and cytokine release
*NF-kB↓,
*NO↓,
*Casp3↓,
*MMP3↓,
*MMP9↓,
*MMP↑, resveratrol attenuated ROS production and mitochondrial membrane-potential disruption; moreover, it restored the normal levels of glutathione (GSH) depleted by Aβ1-42
*GSH↑,
*other↑, resveratrol significantly increased cerebral blood flow (CBF) in the frontal cortex of young healthy humans.
*BioAv↑, receiving 200 mg/day of resveratrol in a formulation with quercetin 320 mg [53], in order to increase its bioavailability,
*memory↑, Resveratrol supplementation induced retention of memory and improved the functional connectivity between the hippocampus and frontal, parietal, and occipital areas, compared with placebo
*GlutMet↑, Also, glucose metabolism was improved and this may account for some of the beneficial effects of resveratrol on neuronal function.
*BioAv↓, The main problems related to the therapeutic or preventive use of resveratrol are linked to its low oral bioavailability and its short half-life in serum
*Half-Life↓,
*toxicity∅, On the other hand, the tolerability and safety profile of resveratrol is very high

3066-

RES,

Resveratrol triggers ER stress-mediated apoptosis by disrupting N-linked glycosylation of proteins in ovarian cancer cells

GSK‐3β↑, resveratrol suppressed the hexosamine biosynthetic pathway and interrupted protein glycosylation through GSK3β activation
Akt↓, Akt attenuation in response to resveratrol.
CHOP↑, Resveratrol-mediated disruption of protein glycosylation induced cellular apoptosis as indicated by the up-regulation of GADD153, followed by the activation of ER-stress sensors (PERK and ATF6α).
ER Stress↑,
PERK↑,
ATF6↑,
UPR↑, Disruption of protein glycosylation causes the accumulation of aberrant of proteins in the endoplasmic reticulum (ER) which in turn activates unfolded protein responses (UPR) in the ER, leading to severe stressful conditions
GlucoseCon↓, Previous studies have shown that resveratrol (RSV) impairs glucose consumption via Akt/GLUT1 axis in cancer [

4666-

RES,

Structural modification of resveratrol analogue exhibits anticancer activity against lung cancer stem cells via suppression of Akt signaling pathway

in-vitro,

Lung,

H23

in-vitro,

Lung,

H292

in-vitro,

Lung,

A549

CSCs↓, we discovered the CSC-targeting activity of resveratrol (RES) analog moscatilin (MOS)
eff↑, Compared with RES, its analog MOS more effectively inhibited cell viability, colony formation, and induced apoptosis in all lung cancer cell lines (H23, H292, and A549).
Akt↓, MOS exerted its anti-CSC effects by inhibiting Akt and consequently restored the activation of glycogen synthase kinase 3β (GSK-3β) and decreased the pluripotent transcription factors (Sox2 and c-Myc).
GSK‐3β↑,
SOX2↓,
cMyc↓,
TumCCA↑, improved activation of various mechanism, such as cell cycle arrest at G2/M phase, production of ROS-mediated apoptosis, and inhibition of Akt activation.
ROS↑,
Apoptosis↑,

5123-

Sal,

Salinomycin suppresses LRP6 expression and inhibits both Wnt/β-catenin and mTORC1 signaling in breast and prostate cancer cells

in-vitro,

BC,

MCF7

in-vitro,

Pca,

PC3

in-vitro,

Pca,

DU145

in-vitro,

BC,

MDA-MB-231

in-vitro,

Nor,

HEK293

Wnt↓, salinomycin was not only a potent Wnt/β-catenin signaling inhibitor, bus also a strong mTORC1 signaling antagonist in breast and prostate cancer cells.
β-catenin/ZEB1↓,
mTORC1↓, SALINOMYCIN INHIBITS MTORC1 SIGNALING IN BREAST AND PROSTATE CANCER CELLS
GSK‐3β↑, Mechanistically, salinomycin activated GSK3β in cancer cells.
cycD1/CCND1↓, salinomycin was able to suppress the expression of cyclin D1 and survivin, two targets of both Wnt/β-catenin and mTORC1 signaling, in prostate and breast cancer cells,
survivin↓,
LRP6↓, SALINOMYCIN INHIBITS LRP6 EXPRESSION AND WNT/β-CATENIN SIGNALING IN BREAST CAND PROSTATE CANCER CELLS
TumCG↓, SALINOMYCIN INHIBITS BREAST AND PROSTATE CANCER CELL GROWTH AND INDUCES CANCER CELL APOPTOSIS
Apoptosis↑,

3048-

SK,

Shikonin inhibits triple-negative breast cancer-cell metastasis by reversing the epithelial-to-mesenchymal transition via glycogen synthase kinase 3β-regulated suppression of β-catenin signaling

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

4T1

in-vitro,

Nor,

MCF12A

in-vivo,

NA,

tumCV↓, results revealed that shikonin potently decreased the viabilities of TNBC MDA-MB-231 and 4T1 cells but showed less cytotoxicity to normal mammary epithelial MCF-12A cells
selectivity↑,
EMT↓, shikonin reversed the epithelial-to-mesenchymal transition (EMT) in MDA-MB-231 and 4T1 cells.
TumCMig↓, Shikonin depressed cell migration and invasion, upregulated E-cadherin levels, downregulated N-cadherin, vimentin, and Snail levels, and reorganized the cytoskeletal proteins F-actin and vimentin.
TumCI↓,
E-cadherin↑,
N-cadherin↓,
Vim↓,
Snail↓,
β-catenin/ZEB1↓, Shikonin reversed EMT by inhibiting activation of β-catenin signaling through attenuating β-catenin expression
GSK‐3β↑, shikonin upregulated glycogen synthase kinase 3β (GSK-3β) levels, leading to enhanced phosphorylation and decreased levels of β-catenin.

2119-

TQ,

Dual properties of Nigella Sativa: anti-oxidant and pro-oxidant

Review,

Var,

*ROS↓, NS has both anti-oxidant and pro-oxidant properties in different cell types hence should be used carefully because it acts as a cytoprotective or cytotoxic agent in inflammatory and malignant conditions respectively.
ROS↑, malignant conditions
chemoP↑, It is reported that nigella can reduce the toxic effects of anticancer drugs
RenoP↑, NS has been shown to improve multiple organ toxicity in models of oxidative stress
hepatoP↑,
NLRP3↓, NLRP3 inflammasome was inactivated partially by inhibition of ROS in melanoma cells by TQ administration.
neuroP↑, NS oil has been found to be neuroprotective against oxidative stress in epileptogenesis
NF-kB↓, TQ has been shown to exhibit down regulation of NF-κB expression in lung cancer cells and in osteosarcoma cells
P21↑, TQ up regulated the expression of p21 and down regulated the histone deacetylase (HDAC) activity and induced histone hyperacetylation causing induction of apoptosis and inhibition of proliferation in pancreatic cancer cell
HDAC↓,
Apoptosis↑,
TumCP↓,
GSH↓, TQ was found to decrease glutathione (GSH) levels in prostate cancer cells resulting in up-regulated expression of GADD45 alpha
GADD45A↑,
GSK‐3β↑, TQ caused the apoptosis of tumor cells by modulation of wnt signaling through activation of GSK-3β

2106-

TQ,

Cancer: Thymoquinone antioxidant/pro-oxidant effect as potential anticancer remedy

Review,

Var,

Apoptosis↑, The anticancer power of TQ is accomplished by several aspects; including promotion of apoptosis, arrest of cell cycle and ROS generation.
TumCCA↑,
ROS↑,
*Catalase↑, activation of antioxidant cytoprotective enzymes including, CAT, SOD, glutathione reductase (GR) [80], glutathione-S-transferase (GST) [81] and glutathione peroxidase (GPx) - scavenging H2O2 and superoxide radicals and preventing lipid peroxidation
*SOD↑,
*GR↑,
*GSTA1↓,
*GPx↑,
*H2O2↓,
*ROS↓,
*lipid-P↓,
*HO-1↑, application of TQ to HaCaT (normal) cells promoted the expression of HO-1 in a concentration and time-dependent pattern
p‑Akt↓, TQ could induce ROS which provoked phosphorylation and activation of Akt and AMPK-α
AMPKα↑,
NK cell↑, TQ was outlined to enhance natural killer (NK) cells activity
selectivity↑, Many researchers have noticed that the growth inhibitory potential of TQ is particular to cancer cells
Dose↝, Moreover, TQ has a dual effect in which it can acts as both pro-oxidant and antioxidant in a dose-dependent manner; it acts as an antioxidant at low concentration whereas, at higher concentrations it possess pro-oxidant property
eff↑, Pro-oxidant property of TQ occurs in the presence of metal ions including copper and iron which induce conversion of TQ into semiquinone. This leads to generation of reactive oxygen species (ROS) causing DNA damage and induction of cellular apoptosis
GSH↓, TQ for one hour resulted in three-fold increase of ROS while reduced GSH level by 60%
eff↓, pre-treatment of cells with N-acetylcysteine, counteracted TQ-induced ROS production and alleviated growth inhibition
P53↑, TQ provokes apoptosis in MCF-7 cancer cells by up regulating the expression of P53 by time-dependent manner.
p‑STAT3↓, TQ inhibited the phosphorylation of STAT3
PI3K↑, via up regulation of PI3K and MPAK signalling pathway
MAPK↑,
GSK‐3β↑, TQ produced apoptosis in cancer cells and modulated Wnt signaling by activating GSK-3β, translocating β-catenin
ChemoSen↑, Co-administration of TQ and chemotherapeutic agents possess greater cytotoxic influence on cancer cells.
RadioS↑, Treatment of cells with both TQ and IR enhanced the antiproliferative power of TQ as observed by shifting the IC50 values for MCF7 and T47D cells from ∼104 and 37 μM to 72 and 18 μM, respectively.
BioAv↓, TQ cannot be used as the primary therapeutic agent because of its poor bioavailability [177,178] and lower efficacy
NRF2↑, TQ to HaCaT cells promoted the expression of HO-1 in a concentration and time-dependent pattern. This was achieved via increasing stabilization of Nrf2

Showing Research Papers: 1 to 26 of 26

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 26

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 6, Catalase↑, 1, GPx↑, 2, GSH↑, 2, GSTA1↓, 1, H2O2↓, 1, HO-1↑, 2, lipid-P↓, 3, MDA↓, 1, NRF2↑, 3, ROS↓, 6, ROS↑, 1, SOD↑, 2,

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↑, 1, MMP∅, 1, MPT↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 2, GlutMet↑, 1, SIRT1↑, 1,

Cell Death(tgid=5) ⓘ

Akt↑, 1, p‑Akt↑, 1, BAX↓, 1, Bcl-2∅, 1, Casp3↓, 1, Cyt‑c↑, 1, MAPK↓, 1,

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1, other↝, 1,

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ERK↓, 1, GSK‐3β↓, 1, GSK‐3β↑, 2, p‑GSK‐3β↑, 3, PI3K↑, 1,

Migration(tgid=13) ⓘ

MMP3↓, 1, MMP9↓, 1, VCAM-1↓, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 1,

Barriers & Transport(tgid=15) ⓘ

BBB↑, 3,

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2↓, 1, ICAM-1↓, 1, IL1β↓, 1, IL4↓, 1, IL6↓, 2, Inflam↓, 5, Inflam↑, 1, MUC2↓, 1, NF-kB↓, 3, PGE2↓, 2,

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 2, tau↓, 2, p‑tau↓, 1,

Protein Aggregation(tgid=19) ⓘ

AGEs↓, 1, Aβ↓, 1, NLRP3↓, 1,

Hormonal & Nuclear Receptors(tgid=20) ⓘ

GR↑, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1, BioAv↑, 3, eff↓, 1, eff↑, 1, Half-Life↓, 1,

Clinical Biomarkers(tgid=22) ⓘ

IL6↓, 2, MUC19↓, 1,

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1, cardioP↑, 1, cognitive↑, 3, memory↑, 2, neuroP↑, 6, toxicity∅, 1,

Infection & Microbiome(tgid=24) ⓘ

AntiFungal↑, 1, AntiViral↑, 1, Bacteria↓, 1,
Total Targets: 71

Scientific Paper Hit Count for: GSK‐3β, Glycogen synthase kinase (GSK)3β

3 Resveratrol
2 Fisetin
2 Magnetic Fields
2 Nimbolide
2 Thymoquinone
1 1,8-Cineole
1 Astaxanthin
1 Baicalein
1 Brucea javanica
1 Caffeic Acid Phenethyl Ester (CAPE)
1 Carvacrol
1 Chrysin
1 Cinnamon
1 Curcumin
1 Deguelin
1 diet FMD Fasting Mimicking Diet
1 Chemotherapy
1 EGCG (Epigallocatechin Gallate)
1 Juglone
1 salinomycin
1 Shikonin

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#:%  Target#:385  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

GSK‐3β Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Protein Aggregation(tgid=19) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Protein Aggregation(tgid=19) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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