General Information:

Id: 6,302
Diseases: Breast cancer - [OMIM]
Homo sapiens
L02 and HepG2 liver hepatocellular cells
article/cited
Reference: Zhang W et al.(2016) Tris(2-chloroethyl)phosphate-induced cell growth arrest via attenuation of SIRT1-independent PI3K/Akt/mTOR pathway J Appl Toxicol 36: 914-924 [PMID: 26378621]

Interaction Information:

Comment TCEP (Tris(2-chloroethyl)phosphate) reduced the cell viability of L02 and HepG2 cells, induced the cell growth arrest, upregulated mRNA and protein levels of SIRT1, and attenuated the PI3K/Akt/mTOR pathway.
Formal Description
Interaction-ID: 59023

drug/chemical compound

Tris(2-chloroethyl)phosphate

decreases_activity of

process

cell viability

in L02 and HepG2 cells
Comment TCEP (Tris(2-chloroethyl)phosphate) reduced the cell viability of L02 and HepG2 cells, induced the cell growth arrest, upregulated mRNA and protein levels of SIRT1, and attenuated the PI3K/Akt/mTOR pathway.
Formal Description
Interaction-ID: 60204

drug/chemical compound

Tris(2-chloroethyl)phosphate

increases_activity of

process

cell quiescence

in L02 and HepG2 cells
Comment TCEP (Tris(2-chloroethyl)phosphate) reduced the cell viability of L02 and HepG2 cells, induced the cell growth arrest, upregulated mRNA and protein levels of SIRT1, and attenuated the PI3K/Akt/mTOR pathway.
Formal Description
Interaction-ID: 60205

drug/chemical compound

Tris(2-chloroethyl)phosphate

increases_expression of

gene/protein

SIRT1

in L02 and HepG2 cells; upregulated mRNA and protein levels of SIRT1
Comment TCEP (Tris(2-chloroethyl)phosphate) reduced the cell viability of L02 and HepG2 cells, induced the cell growth arrest, upregulated mRNA and protein levels of SIRT1, and attenuated the SIRT1-independent PI3K/Akt/mTOR pathway.
Formal Description
Interaction-ID: 60206

drug/chemical compound

Tris(2-chloroethyl)phosphate

decreases_activity of

process

PI3K/AKT/TOR signaling

in L02 and HepG2 cells
Comment TCEP (Tris(2-chloroethyl)phosphate) reduced the cell viability of L02 and HepG2 cells, induced the cell growth arrest, upregulated mRNA and protein levels of SIRT1, and attenuated the SIRT1-independent PI3K/Akt/mTOR pathway. The growth arrest of the L02 and HepG2 cells were aggravated after inhibiting the SIRT1 expression with EX-527. The findings above suggested that TCEP induced the cell growth arrest of L02 and HepG2 cells via attenuation of the SIRT1-independent PI3K/Akt/mTOR pathway.
Formal Description
Interaction-ID: 60209

gene/protein

SIRT1

NOT affects_activity of

process

PI3K/AKT/TOR signaling

in L02 and HepG2 cells
Comment The growth arrest of the L02 and HepG2 cells were aggravated after inhibiting the SIRT1 expression with EX-527. The findings above suggested that TCEP induced the cell growth arrest of L02 and HepG2 cells via attenuation of the SIRT1-independent PI3K/Akt/mTOR pathway. EX-527, an inhibitor of SIRT1, inhibited the expression of SIRT1.
Formal Description
Interaction-ID: 60210

drug/chemical compound

EX-527

decreases_activity of

gene/protein

SIRT1

in L02 and HepG2 cells
Comment SIRT1 overexpression not only promoted mitotic entry of liver cells, cell growth and proliferation, but also protected cells from apoptosis through activation of the PTEN/PI3K/Akt pathway (cited information).
Formal Description
Interaction-ID: 60211

gene/protein

SIRT1

increases_activity of

process

PTEN/PI3K/AKT signaling

if SIRT1 is overexpressed, resulting in a protection of the cells from apoptosis.
Comment SIRT1 overexpression negatively regulated the mTOR pathway by the TSC1/2 complex in mouse embryonic fibroblasts and HeLa cells (cited information). In other experiments SIRT1 potentially regulated mTOR signaling using a negative-feedback loop. SIRT1 overexpression can intensify its interaction with mTOR signaling, and then regulate cell metabolism, growth or survival. SIRT1 overexpression promoted cell survival through inhibiting mTOR signaling (cited information).
Formal Description
Interaction-ID: 60212

gene/protein

SIRT1

decreases_activity of

process

TOR signaling

in mouse embryonic fibroblasts and HeLa cells; if SIRT1 is overexpressed, via TSC1-TSC2 complex.
Comment SIRT1 inhibited cell proliferation in vitro and tumor formation in colon cancer (cited information).
Formal Description
Interaction-ID: 60213

gene/protein

SIRT1

decreases_activity of

in vitro and tumor formation in colon cancer
Comment TCEP downregulated PI3K, p-PI3K, Akt, p-Akt, mTOR and p-mTOR proteins in L02 cells and HepG2 cells. Downregulated PI3K, p-PI3K, Akt, p-Akt, mTOR and p-mTOR proteins in L02 and HepG2 cells were observed in all co-treatment groups of TCEP with EX-527.
Formal Description
Interaction-ID: 60216

drug/chemical compound

Tris(2-chloroethyl)phosphate

decreases_activity of

complex/PPI

Phosphatidylinositol 3-kinase

in L02 cells and HepG2 cells; of PI3K and p-PI3K proteins, also in all co-treatment groups of TCEP with EX-527.
Comment SIRT1 activation by resveratrol caused inhibition of cell growth by inducing cell cycle arrest, and thereby reduced tumor formation in a breast cancer model (cited information).
Formal Description
Interaction-ID: 60219

drug/chemical compound

Resveratrol

increases_activity of

gene/protein

SIRT1

resulting in an inhibition of cell growth by inducing cell cycle arrest.
Drugbank entries Show/Hide entries for Resveratrol
Comment SIRT1 overexpression not only promoted mitotic entry of liver cells, cell growth and proliferation, but also protected cells from apoptosis through activation of the PTEN/PI3K/Akt pathway (cited information).
Formal Description
Interaction-ID: 60350

gene/protein

SIRT1

increases_activity of

process

mitotic entry

of liver cells; if SIRT1 is overexpressed.
Comment SIRT1 overexpression not only promoted mitotic entry of liver cells, cell growth and proliferation, but also protected cells from apoptosis through activation of the PTEN/PI3K/Akt pathway (cited information).
Formal Description
Interaction-ID: 60351

gene/protein

SIRT1

increases_activity of

process

cell growth

if SIRT1 is overexpressed.
Comment SIRT1 overexpression not only promoted mitotic entry of liver cells, cell growth and proliferation, but also protected cells from apoptosis through activation of the PTEN/PI3K/Akt pathway (cited information).
Formal Description
Interaction-ID: 60352

gene/protein

SIRT1

increases_activity of

if SIRT1 is overexpressed.
Comment SIRT1 overexpression not only promoted mitotic entry of liver cells, cell growth and proliferation, but also protected cells from apoptosis through activation of the PTEN/PI3K/Akt pathway (cited information).
Formal Description
Interaction-ID: 60353

gene/protein

SIRT1

decreases_activity of

if SIRT1 is overexpressed through activation of the PTEN/PI3K/Akt pathway.
Comment SIRT1 overexpression negatively regulated the mTOR pathway by the TSC1/2 complex in mouse embryonic fibroblasts and HeLa cells (cited information).
Formal Description
Interaction-ID: 60354

gene/protein

SIRT1

affects_activity of

complex/PPI

TSC1-TSC2 complex

in mouse embryonic fibroblasts and HeLa cells; if SIRT1 is overexpressed, resulting in a negative regulation the mTOR pathway.
Comment TCEP downregulated PI3K, p-PI3K, Akt, p-Akt, mTOR and p-mTOR proteins in L02 cells and HepG2 cells. Downregulated PI3K, p-PI3K, Akt, p-Akt, mTOR and p-mTOR proteins in L02 and HepG2 cells were observed in all co-treatment groups of TCEP with EX-527.
Formal Description
Interaction-ID: 60355

drug/chemical compound

Tris(2-chloroethyl)phosphate

decreases_activity of

gene/protein

AKT1

in L02 cells and HepG2 cells; of AKT and p-AKT proteins, also in all co-treatment groups of TCEP with EX-527.
Drugbank entries Show/Hide entries for AKT1
Comment TCEP downregulated PI3K, p-PI3K, Akt, p-Akt, mTOR and p-mTOR proteins in L02 cells and HepG2 cells. Downregulated PI3K, p-PI3K, Akt, p-Akt, mTOR and p-mTOR proteins in L02 and HepG2 cells were observed in all co-treatment groups of TCEP with EX-527.
Formal Description
Interaction-ID: 60356

drug/chemical compound

Tris(2-chloroethyl)phosphate

decreases_activity of

gene/protein

MTOR

in L02 cells and HepG2 cells; of mTOR and p-mTOR proteins, also in all co-treatment groups of TCEP with EX-527.
Drugbank entries Show/Hide entries for MTOR
Comment SIRT1 activation by resveratrol caused inhibition of cell growth by inducing cell cycle arrest, and thereby reduced tumor formation in a breast cancer model (cited information).
Formal Description
Interaction-ID: 60357

gene/protein

SIRT1

decreases_activity of

process

cell growth

by inducing cell cycle arrest.
Comment SIRT1 activation by resveratrol caused inhibition of cell growth by inducing cell cycle arrest, and thereby reduced tumor formation in a breast cancer model (cited information).
Formal Description
Interaction-ID: 60358

gene/protein

SIRT1

increases_activity of

Comment SIRT1 activation by resveratrol caused inhibition of cell growth by inducing cell cycle arrest, and thereby reduced tumor formation in a breast cancer model (cited information).
Formal Description
Interaction-ID: 60359

gene/protein

SIRT1

decreases_activity of

disease

Breast cancer

reducing tumor formation in a breast cancer model.