TSC2 Cancer Research Results
TSC2, tuberous sclerosis complex (TSC): Click to Expand ⟱
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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.
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Scientific Papers found: Click to Expand⟱
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/ATG6↑, 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
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in-vitro, |
GBM, |
U87MG |
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in-vitro, |
GBM, |
U251 |
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in-vitro, |
GBM, |
GL26 |
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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
Bcl-2↓,
BAX↑,
Akt↓,
p70S6↓,
PTEN↑,
TSC2↑,
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/ABCB1↓, 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/PTGS2↓, 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
mt-Apoptosis↑, licochalcones can activate the mitochondrial apoptosis pathway and the death receptor pathway, promote autophagy-related protein expression, inhibit cell cycle protein expression,
TumAuto↑,
TumCMig↓, regulate cancer migration-related protein expression via multiple signaling pathways, including EGFR/ERK, PI3K/Akt/mTOR, p38/JNK, JAK2/STAT3, MEK/ERK, Wnt/β-catenin, and MKK4/JNK signaling pathways.
LC3‑Ⅱ/LC3‑Ⅰ↑, increasing the LC3-II/LC3-I ratio, as well as the levels of the autophagy-related proteins ATG5, ATG7, and P62.
ATG5↑,
ATG7↑,
p62↑,
CHOP/DDIT3↑, LA-induced increases in CHOP expression also promote autophagy
ER Stress↑, LA-induced autophagy in lung cancer cells is associated with the induction of endoplasmic reticulum stress
UPR↑, LA (10 μM) enhances the expression of miR-144-3p, causes unfolded protein response,
ATG3↑, triggers autophagy by promoting the accumulation and expression of ATG1, ATG3, ATG6, and ATG16 via activation of the PERK/ATF4/CHOP signaling pathway
Beclin-1/ATG6↑,
ATG16L1↑,
PERK↑,
ATF4↑,
ATP↓, LA (2.5–25 μM) inhibited ATP production and caused mitochondrial dysfunction in H1299 and H322 lung cancer cells by inhibiting hypoxia-induced HIF-1α accumulation and the expression of target genes GLUT1 and PDK1
Hif1a↓,
GLUT1↓,
PDK1 / PDPK1↓,
Bcl-xL↓, induce apoptosis in H460 and A549 lung cancer cells by decreasing the levels of Bcl-xL and Bcl-2 while increasing the levels of Bad, Bax, cleaved PARP, and caspase-3
Bcl-2↓,
BAD↑,
BAX↑,
Casp3↑,
survivin↓, LA (5–50 μM) downregulated the expression of survivin by inhibiting the EGFR signaling pathway and its downstream kinases ERK1/2 and AKT in H3255, HCC827, H1975, and A549 lung cancer cells
EGFR↓,
ERK↓,
Akt↓,
mtDam↑, LB (5–15 μM) inhibited the EGFR and MET signaling pathways and induced mitochondrial dysfunction and endoplasmic reticulum stress in HCC827 lung cancer cells, which induced the loss of MMP, release of cytochrome c, and increased expression of casp
MMP↓,
Cyt‑c↑,
Casp↑,
MDM2↓, By inhibiting the expression of MDM2, cyclin B1, CDC2, and CDC25C, LA (10–15 μM) led to cell cycle arrest of H460 and A549 lung cancer cells at the G2/M phase
CycB/CCNB1↓,
CDC2↓,
CDC25↓,
TumCCA↑,
TumCP↓, decreases in the proliferation of lung cancer cells by LA were related to the inhibition of the Wnt/β-catenin signaling pathway
Wnt↓,
β-catenin/ZEB1↓,
Sp1/3/4↓, LA (2–20 μM) inhibited the AKT signaling pathway and the expression of the downstream transcription factor Sp1, which reduced the levels of MMP-1 and MMP-3 and inhibited the migration and invasion of A549 and H460 lung cancer cells
MMP-10↓,
MMP3↓,
TumCI↓,
Imm↑, Activation of the immune system
PD-L1↓, LA (10–50 μM) inhibited the expression of PD-L1 and thereby induced the production of reactive oxygen species (ROS) in A549 lung cancer cells, which inhibited the phosphorylation of 4EBP1, activated the PERK/eIF2α pathway,
ROS↑,
4E-BP1↓,
eIF2α↓,
PI3K↓, By inhibiting the PI3K/Akt/mTOR signaling pathway, LA (5–20 μM) activated the mitochondrial apoptosis pathway
mTOR↓,
p‑cMET↑, LA (1–50 μM) induced endoplasmic reticulum stress in HepG2 cells by inducing phosphorylation of VEGFR2, c-Met receptor, and PLCγ1 and enhancing the cytosolic Ca2+ release from the endoplasmic reticulum, which subsequently induced ROS accumulation
Ca+2↑,
RUBCN↓, LA-induced (5–50 μM) downregulation of PDK1 and rubicon by activating the ULK1/Atg13 signaling pathway and increasing the expression of TSC1/2, PRAS40, CTMP, and PP2A.
ATG13↑,
TSC1↑,
TSC2↑,
PRAS40↑,
PP2A↑,
ULK1/ATG1↑,
THEM4/CTMP↑,
DR5↑, LA activates the death receptor pathway and caspase cascade by increasing the expression of DR3, DR5, and Fas.
Fas↑,
TNFRSF25/DR3/APO3/LARD/TRAMP/WSL1↑,
PKCδ↓, LA also decreases the expression of the survival factor PKCε, p70S6K, and Akt.
P70S6K↓,
VEGF↓, Via downregulation of VEGF-A, LE (7–14 mg/kg) inhibited angiogenesis in cancer tissue in a xenograft mouse model using MDA-MB 231 breast cancer cells
angioG↓,
HK2↓, Moreover, the inhibitory effect of LA (10–50 μM) on the AKT signaling pathway can downregulate the expression of hexokinase 2A and inhibit glycolysis, thereby inducing apoptosis of MKN45 and SGC7901 cells
Glycolysis↓,
TrxR1↓, LA (10–40 μM) can enhance the production of intracellular ROS by inhibiting the expression of thioredoxin reductase-1, which activates the mitochondrial apoptosis pathway and induces apoptosis in HCT-116 cells
APAF1↑, By increasing intracellular Ca2+ and ROS levels, decreasing mitochondrial membrane potential, upregulating Apaf-1, caspase-9, caspase-3, and cleaved PARP levels, and elevating the Bax/Bcl-2 ratio, LA (10–80 μM) induced T24 cells apoptosis
cl‑PARP↑,
Bax:Bcl2↑,
ABCG2↓, By reducing the expression of BCRP, LA (10–100 μM) reduced the BCRP-mediated efflux of doxorubicin and temozolomide in BCRP-MDCKII cells.
BioEnh↑, Inhibition of BCRP expression can promote increased intestinal (re)uptake of antineoplastic drugs and decrease their hepatic metabolization, thereby enhancing their bioavailability.
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in-vitro, |
Ovarian, |
SKOV3 |
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TumCMig↓,
TumCI↓,
MDA↑,
ROS↑,
BAX↑,
Casp3↑,
Bcl-2↓,
SREBP1/SREBF1↓,
FASN↓,
AMPK↓,
p‑AMPK↑,
p‑P53↑,
p‑TSC2↑,
p‑Akt↓,
p‑mTOR↓,
p‑S6K↓, p-S6K1
p‑4E-BP1↓,
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in-vitro, |
Pca, |
PC3 |
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in-vitro, |
Pca, |
DU145 |
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in-vitro, |
Pca, |
LNCaP |
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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.
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in-vitro, |
Colon, |
Caco-2 |
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Dose↝, Vitexin exhibited an IC50 of 38.01 ± 0.64 μg/mL against Caco-2 cells.
tumCV↓, vitexin at the specified concentrations for 48 hours resulted in a significant decrease in cell viability by 28.40%, with inhibitory rates reaching 71.6%.
SOD↓, vitexin significantly inhibited SOD and CAT activities while enhancing MDA production.
Catalase↓,
MDA↑,
P53↑, vitexin treatment upregulated the expression of key apoptotic markers (P53, Bax, TSC2, Sestrin 2, and PUMA) and the expression of AMPK, PI3K, and Akt
BAX↓,
TSC2↑,
SESN2↑,
PUMA↑,
AMPK↑,
PI3K↑,
Akt↑,
mTOR↓, while downregulating mTOR genes and proteins,
Showing Research Papers: 1 to 8 of 8
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8
Pathway results for Effect on Cancer / Diseased Cells:
NA, unassigned(tgid=0) ⓘ
ATG13↑, 1, ATG16L1↑, 1, RUBCN↓, 1, THEM4/CTMP↑, 1, TNFRSF25/DR3/APO3/LARD/TRAMP/WSL1↑, 1, ULK1/ATG1↑, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
Catalase↓, 1, HO-1↑, 1, lipid-P↓, 1, MDA↑, 2, ROS↓, 1, ROS↑, 4, SOD↓, 1, TrxR1↓, 1,
Mitochondria & Bioenergetics(tgid=3) ⓘ
ATP↓, 1, BCR↓, 1, CDC16↓, 1, CDC2↓, 1, CDC25↓, 1, EGF↓, 1, MMP↓, 2, mtDam↑, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
AKT1↓, 1, AMPK↓, 1, AMPK↑, 2, p‑AMPK↑, 1, ATG7↑, 2, cMyc↓, 1, FASN↓, 1, Glycolysis↓, 1, HK2↓, 1, PDK1 / PDPK1↓, 1, p‑S6K↓, 1, SREBP1/SREBF1↓, 1,
Cell Death(tgid=5) ⓘ
Akt↓, 4, Akt↑, 1, p‑Akt↓, 1, APAF1↑, 1, Apoptosis↑, 2, mt-Apoptosis↑, 1, BAD↑, 1, BAX↓, 1, BAX↑, 4, Bax:Bcl2↑, 1, Bcl-2↓, 5, Bcl-xL↓, 1, Casp↑, 1, Casp3↑, 2, cl‑Casp3↑, 1, cl‑Casp9↑, 1, CBP↑, 1, Cyt‑c↑, 2, DR5↑, 1, Fas↑, 1, MDM2↓, 1, PUMA↑, 1, survivin↓, 1,
Kinase & Signal Transduction(tgid=6) ⓘ
AMPKα↑, 1, CDC7↓, 1, HER2/EBBR2↓, 1, p70S6↓, 2, Sp1/3/4↓, 1, TSC2↑, 7, p‑TSC2↑, 1,
Transcription & Epigenetics(tgid=7) ⓘ
cJun↓, 1, tumCV↓, 2,
Protein Folding & ER Stress(tgid=8) ⓘ
CHOP/DDIT3↑, 1, eIF2α↓, 1, ER Stress↑, 2, GRP78/BiP↑, 1, HSF1↓, 1, HSP70/HSPA5↑, 1, IRE1↑, 1, PERK↑, 1, UPR↑, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
ATG3↑, 1, ATG5↑, 1, Beclin-1/ATG6↑, 2, LC3‑Ⅱ/LC3‑Ⅰ↑, 1, p62↑, 1, SESN2↑, 1, TumAuto↑, 2,
DNA Damage & Repair(tgid=10) ⓘ
BRCA1↑, 1, CUL4B↑, 1, DNAdam↑, 1, P53↓, 1, P53↑, 2, p‑P53↑, 1, cl‑PARP↑, 1, PCNA↓, 1,
Cell Cycle & Senescence(tgid=11) ⓘ
CDK2↓, 2, CDK4↓, 1, CycB/CCNB1↓, 1, cycD1/CCND1↓, 2, cycE/CCNE↓, 2, cycF↓, 1, E2Fs↓, 1, P21↑, 2, RB1↑, 1, TumCCA↑, 4,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
4E-BP1↓, 1, p‑4E-BP1↓, 1, cDC2↓, 1, cFos↓, 1, p‑cMET↑, 1, EMT↓, 1, EP300↑, 1, ERK↓, 2, mTOR↓, 5, p‑mTOR↓, 1, mTORC1↓, 1, mTORC2↓, 1, NF2↑, 1, P70S6K↓, 1, p85S6K↓, 1, PI3K↓, 3, PI3K↑, 1, PTEN↑, 2, TCF-4↓, 1, TumCG↓, 1, Wnt↓, 2,
Migration(tgid=13) ⓘ
AP-1↓, 1, Ca+2↑, 1, CDK4/6↓, 1, MMP-10↓, 1, MMP3↓, 1, MMP7↓, 1, MMP9↓, 1, MSH2↑, 1, PKCδ↓, 1, TGF-β↓, 1, TSC1↑, 2, TumCA↓, 1, TumCI↓, 3, TumCMig↓, 3, TumCP↓, 2, uPA↓, 1, β-catenin/ZEB1↓, 2,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↓, 1, ATF4↑, 2, EGFR↓, 2, Hif1a↓, 1, VEGF↓, 1,
Barriers & Transport(tgid=15) ⓘ
GLUT1↓, 1, P-gp/ABCB1↓, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
COX2/PTGS2↓, 1, Imm↑, 1, NF-kB↓, 1, PD-L1↓, 1,
Protein Aggregation(tgid=19) ⓘ
PP2A↑, 1,
Hormonal & Nuclear Receptors(tgid=20) ⓘ
AR↓, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
ABCG2↓, 1, BioEnh↑, 1, ChemoSen↑, 1, Dose↝, 1, eff↓, 1, eff↑, 2, RadioS↑, 1,
Clinical Biomarkers(tgid=22) ⓘ
AR↓, 1, BRCA1↑, 1, EGFR↓, 2, HER2/EBBR2↓, 1, PD-L1↓, 1,
Functional Outcomes(tgid=23) ⓘ
chemoPv↑, 1, PRAS40↑, 1, TGFβR1↑, 1,
Total Targets: 166
Pathway results for Effect on Normal Cells:
Total Targets: 0
Scientific Paper Hit Count for: TSC2, tuberous sclerosis complex (TSC)
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
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