TSC2 Cancer Research Results

TSC2, tuberous sclerosis complex (TSC): Click to Expand ⟱
Source:
Type:
TSC2 is a tumor suppressor gene as well as a disease-causing gene for autosomal dominant disorder tuberous sclerosis complex (TSC).

TSC1 (hamartin) and TSC2 (tuberin) form a complex that plays a critical role in regulating the mTOR (mechanistic target of rapamycin) pathway.
• The TSC1/TSC2 complex acts as a negative regulator of mTOR signaling; when active, it helps suppress cell growth and proliferation.

TSC1 and TSC2 serve as tumor suppressors.
TSC1 and TSC2 are not overexpressed in cancer; they are typically involved in loss-of-function scenarios that lead to tumorigenesis.
Scientific Papers found: Click to Expand⟱
250- AL,    Allicin Induces p53-Mediated Autophagy in Hep G2 Human Liver Cancer Cells
- in-vitro, Liver, HepG2
P53↓, allicin decreased the level of cytoplasmic p53, the PI3K/mTOR signaling pathway
PI3K↓, decreased the levels of PI3K/mTOR, p-Bcl-2, Bcl-xL, and cytoplasmic p53 in Hep G2 cells.
mTOR↓,
Bcl-2↓,
AMPK↑,
TSC2↑,
Beclin-1↑, llicin increased the levels of Beclin-1, Bad, p-AMPK, TSC2, and Atg7
TumAuto↑, Allicin induced autophagy and increased the formation of autophagosomes and autophagolysosomes in Hep G2 cells.
tumCV↓, Allicin treatment at 35 uM decreased the viability of Hep G2 cells after 12 and 24 h significantly.
ATG7↑,
MMP↓, allicin treatment caused a decrease of MMP of Hep G2 cells and degradation of mitochondria

1357- Ash,    Cytotoxicity of withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathways
- in-vitro, GBM, U87MG - in-vitro, GBM, U251 - in-vitro, GBM, GL26
TumCP↓,
TumCCA↑, G2/M cell cycle
Akt↓,
mTOR↓,
p70S6↓,
p85S6K↓,
AMPKα↑,
TSC2↑,
HSP70/HSPA5↑,
HO-1↑,
HSF1↓,
Apoptosis↑,
ROS↑, Withaferin A elevates pro-oxidant potential in GBM cells and induces a cellular oxidative stress response
eff↓, Pre-treatment with a thiol-antioxidant protects GBM cells from the anti-proliferative and cytotoxic effects of withaferin A NAC pretreatment was able to completely prevent cell cycle shift to G2/M arrest following 1µM WA treatment at 24h

750- Bor,    Calcium fructoborate regulate colon cancer (Caco-2) cytotoxicity through modulation of apoptosis
- in-vitro, CRC, Caco-2
Bcl-2↓,
BAX↑,
Akt↓,
p70S6↓,
PTEN↑,
TSC2↑,

2839- FIS,    Dietary flavonoid fisetin for cancer prevention and treatment
- Review, Var, NA
DNAdam↑, Fisetin induced DNA fragmentation, ROS generation, and apoptosis in NCI-H460 cells via a reduction in Bcl-2 and increase in Bax expression
ROS↑,
Apoptosis↑,
Bcl-2↓,
BAX↑,
cl‑Casp9↑, Fisetin treatment increased cleavage of caspase-9 and caspase-3 thereby increasing caspase-3 activation
cl‑Casp3↑,
Cyt‑c↑, leading to cytochrome-c release
lipid-P↓, Fisetin (25 mg/kg body weight) decreased histological lesions and levels of lipid peroxidation and modulated the enzymatic and nonenzymatic anti-oxidants in B(a)P-treated Swiss Albino mice
TumCG↓, We observed that fisetin treatment (5–20 μM) inhibits cell growth and colony formation in A549 NSC lung cancer cells.
TumCA↓, Another study showed that fisetin inhibits adhesion, migration, and invasion in A549 lung cancer cells by downregulating uPA, ERK1/2, and MMP-2
TumCMig↓,
TumCI↓,
uPA↓,
ERK↓,
MMP9↓,
NF-kB↓, Treatment with fisetin also decreased the nuclear levels of NF-kB, c-Fos, c-Jun, and AP-1 and inhibited NF-kB binding.
cFos↓,
cJun↓,
AP-1↓,
TumCCA↑, Our laboratory has previously shown that treatment of LNCaP cells with fisetin caused inhibition of PCa by G1-phase cell cycle arrest
AR↓, inhibited androgen signaling and tumor growth in athymic nude mice
mTORC1↓, induced autophagic cell death in PCa cells through suppression of mTORC1 and mTORC2
mTORC2↓,
TSC2↑, activated the mTOR repressor TSC2, commonly associated with inhibition of Akt and activation of AMPK
EGF↓, Fisetin also inhibits EGF and TGF-β induced YB-1 phosphorylation and EMT in PCa cells
TGF-β↓,
EMT↓, Fisetin also inhibits EGF and TGF-β induced YB-1 phosphorylation and EMT in PCa cells
P-gp↓, decrease the P-gp protein in multidrug resistant NCI/ADR-RES cells.
PI3K↓, Fisetin also inhibited the PI3K/AKT/NFkB signaling
Akt↓,
mTOR↓, Fisetin inhibited melanoma progression in a 3D melanoma skin model with downregulation of mTOR, Akt, and upregulation of TSC
eff↑, combinational treatment study of melatonin and fisetin demonstrated enhanced antitumor activity of fisetin
ROS↓, Fisetin inhibited ROS and augmented NO generation in A375 melanoma cells
ER Stress↑, induction of ER stress evidenced by increased IRE1α, XBP1s, ATF4, and GRP78 levels in A375 and 451Lu cells.
IRE1↑,
ATF4↑,
GRP78/BiP↑,
ChemoSen↑, combination of fisetin with sorafenib effectively inhibited EMT and augmented the anti-metastatic potential of sorafenib by reducing MMP-2 and MMP-9 proteins in melanoma cell xenografts
CDK2↓, Fisetin (0–60 μM) was shown to inhibit activity of CDKs dose-dependently leading to cell cycle arrest in HT-29 human colon cancer cells
CDK4↓, Fisetin treatment decreased activities of CDK2 and CDK4 via decreased levels of cyclin-E, cyclin-D1 and increase in p21 (CIP1/WAF1) levels.
cycE/CCNE↓,
cycD1/CCND1↓,
P21↑,
COX2↓, fisetin (30–120 μM) induces apoptosis in colon cancer cells by inhibiting COX-2 and Wnt/EGFR/NF-kB -signaling pathways
Wnt↓,
EGFR↓,
β-catenin/ZEB1↓, Fisetin treatment inhibited Wnt/EGFR/NF-kB signaling via downregulation of β-catenin, TCF-4, cyclin D1, and MMP-7
TCF-4↓,
MMP7↓,
RadioS↑, fisetin treatment was found to radiosensitize human colorectal cancer cells which are resistant to radiotherapy
eff↑, Combined treatment of fisetin with NAC increased cleaved caspase-3, PARP, reduced mitochondrial membrane potential with induction of caspase-9 in COLO25 cells

1237- PTS,    Pterostilbene induces cell apoptosis and inhibits lipogenesis in SKOV3 ovarian cancer cells by activation of AMPK-induced inhibition of Akt/mTOR signaling cascade
- in-vitro, Ovarian, SKOV3
TumCMig↓,
TumCI↓,
MDA↑,
ROS↑,
BAX↑,
Casp3↑,
Bcl-2↓,
SREBP1↓,
FASN↓,
AMPK↓,
p‑AMPK↑,
p‑P53↑,
p‑TSC2↑,
p‑Akt↓,
p‑mTOR↓,
p‑S6K↓, p-S6K1
p‑4E-BP1↓,

100- QC,    Inhibition of Prostate Cancer Cell Colony Formation by the Flavonoid Quercetin Correlates with Modulation of Specific Regulatory Genes
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145 - in-vitro, Pca, LNCaP
cycD1/CCND1↓, CCND1, CCND2, CCND3
cycE/CCNE↓, CCNE1, CCNE2
CDK2↓,
CDK4/6↓, CDK4, CDK8
E2Fs↓, E2F2, E2F3
PCNA↓,
cDC2↓,
PTEN↑,
MSH2↑,
P21↑,
EP300↑, p300
BRCA1↑,
NF2↑,
TSC1↑,
TGFβR1↑, TGFβR2
P53↑,
RB1↑, Rb
AKT1↓,
cMyc↓,
CDC7↓,
cycF↓, CCNF
CDC16↓,
CUL4B↑, CUL4B, a member of the cullin gene family that is also known to be involved in control of the cell cycle, was significantly up-regulated by quercetin.
CBP↑,
TSC2↑,
HER2/EBBR2↓, erb-2
BCR↓,
TumCCA↑, quercetin significantly inhibited the expression of specific oncogenes and genes controlling G1, S, G2, and M phases of the cell cycle.
chemoPv↑, Our results correlate with those of nutritional studies that support the roles of dietary bioflavonoids as cancer chemopreventive agents.


Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

HO-1↑, 1,   lipid-P↓, 1,   MDA↑, 1,   ROS↓, 1,   ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

BCR↓, 1,   CDC16↓, 1,   EGF↓, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AKT1↓, 1,   AMPK↓, 1,   AMPK↑, 1,   p‑AMPK↑, 1,   ATG7↑, 1,   cMyc↓, 1,   FASN↓, 1,   p‑S6K↓, 1,   SREBP1↓, 1,  

Cell Death ⓘ

Akt↓, 3,   p‑Akt↓, 1,   Apoptosis↑, 2,   BAX↑, 3,   Bcl-2↓, 4,   Casp3↑, 1,   cl‑Casp3↑, 1,   cl‑Casp9↑, 1,   CBP↑, 1,   Cyt‑c↑, 1,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,   CDC7↓, 1,   HER2/EBBR2↓, 1,   p70S6↓, 2,   TSC2↑, 5,   p‑TSC2↑, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   GRP78/BiP↑, 1,   HSF1↓, 1,   HSP70/HSPA5↑, 1,   IRE1↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

BRCA1↑, 1,   CUL4B↑, 1,   DNAdam↑, 1,   P53↓, 1,   P53↑, 1,   p‑P53↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 2,   CDK4↓, 1,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 2,   cycF↓, 1,   E2Fs↓, 1,   P21↑, 2,   RB1↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

p‑4E-BP1↓, 1,   cDC2↓, 1,   cFos↓, 1,   EMT↓, 1,   EP300↑, 1,   ERK↓, 1,   mTOR↓, 3,   p‑mTOR↓, 1,   mTORC1↓, 1,   mTORC2↓, 1,   NF2↑, 1,   p85S6K↓, 1,   PI3K↓, 2,   PTEN↑, 2,   TCF-4↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

AP-1↓, 1,   CDK4/6↓, 1,   MMP7↓, 1,   MMP9↓, 1,   MSH2↑, 1,   TGF-β↓, 1,   TSC1↑, 1,   TumCA↓, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 1,   uPA↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

ATF4↑, 1,   EGFR↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   NF-kB↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↓, 1,   eff↑, 2,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   BRCA1↑, 1,   EGFR↓, 1,   HER2/EBBR2↓, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,   TGFβR1↑, 1,  
Total Targets: 105

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TSC2, tuberous sclerosis complex (TSC)
1 Allicin (mainly Garlic)
1 Ashwagandha(Withaferin A)
1 Boron
1 Fisetin
1 Pterostilbene
1 Quercetin
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#:497  State#:%  Dir#:2
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