scholarly journals Sialyltransferase ST3GAL6 mediates the effect of microRNA-26a on cell growth, migration, and invasion in hepatocellular carcinoma through the protein kinase B/mammalian target of rapamycin pathway

2017 ◽  
Vol 108 (2) ◽  
pp. 267-276 ◽  
Author(s):  
Mingming Sun ◽  
Xuzi Zhao ◽  
Leilei Liang ◽  
Xufeng Pan ◽  
Hao Lv ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Kinase ◽  
Cell Growth ◽  
Protein Kinase B ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Migration And Invasion

Lupeol Inhibits Proliferation and Promotes Apoptosis of Ovarian Cancer Cells by Inactivating Phosphoinositide-3-Kinase/Protein Kinase B/ Mammalian Target of Rapamycin Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 206-210
Author(s):  
Feng Chen ◽  
Bei Zhang
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Protein Kinase ◽  
Cell Viability ◽  
Cancer Cells ◽  
Protein Kinase B ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Ovarian Cancer Cells ◽  
Phosphoinositide 3 Kinase

Lupeol exhibits multiple pharmacological activities including, anticancerous, anti-inflammatory, and antioxidant. The aim of this study was to explore the anticancerous activity of lupeol on ovarian cancer cells and examine its mechanism of action. To this end, increasing concentrations of lupeol on cell viability, cell cycle, and apoptosis in Caov-3 cells were evaluated. Lupeol inhibited cell viability, induced G1 phase arrest in cell cycle, increased cell apoptosis, and inhibited the ratio of phospho-Akt/protein kinase B and phospho-mammalian target of rapamycin/mammalian target of rapamycin. In conclusion, these data suggest that lupeol may play a therapeutic role in ovarian cancer.

scholarly journals Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)

2009 ◽  
Vol 421 (1) ◽  
pp. 29-42 ◽  
Author(s):  
Juan M. García-Martínez ◽  
Jennifer Moran ◽  
Rosemary G. Clarke ◽  
Alex Gray ◽  
Sabina C. Cosulich ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Growth ◽  
Mammalian Target Of Rapamycin ◽  
Specific Inhibitor ◽  
Initiation Factor ◽  
Target Of Rapamycin ◽  
S6 Kinase ◽  
Class 1 ◽  
Hydrophobic Motif ◽  
Ribosomal S6 Kinase

mTOR (mammalian target of rapamycin) stimulates cell growth by phosphorylating and promoting activation of AGC (protein kinase A/protein kinase G/protein kinase C) family kinases such as Akt (protein kinase B), S6K (p70 ribosomal S6 kinase) and SGK (serum and glucocorticoid protein kinase). mTORC1 (mTOR complex-1) phosphorylates the hydrophobic motif of S6K, whereas mTORC2 phosphorylates the hydrophobic motif of Akt and SGK. In the present paper we describe the small molecule Ku-0063794, which inhibits both mTORC1 and mTORC2 with an IC50 of ∼10 nM, but does not suppress the activity of 76 other protein kinases or seven lipid kinases, including Class 1 PI3Ks (phosphoinositide 3-kinases) at 1000-fold higher concentrations. Ku-0063794 is cell permeant, suppresses activation and hydrophobic motif phosphorylation of Akt, S6K and SGK, but not RSK (ribosomal S6 kinase), an AGC kinase not regulated by mTOR. Ku-0063794 also inhibited phosphorylation of the T-loop Thr308 residue of Akt phosphorylated by PDK1 (3-phosphoinositide-dependent protein kinase-1). We interpret this as implying phosphorylation of Ser473 promotes phosphorylation of Thr308 and/or induces a conformational change that protects Thr308 from dephosphorylation. In contrast, Ku-0063794 does not affect Thr308 phosphorylation in fibroblasts lacking essential mTORC2 subunits, suggesting that signalling processes have adapted to enable Thr308 phosphorylation to occur in the absence of Ser473 phosphorylation. We found that Ku-0063794 induced a much greater dephosphorylation of the mTORC1 substrate 4E-BP1 (eukaryotic initiation factor 4E-binding protein 1) than rapamycin, even in mTORC2-deficient cells, suggesting a form of mTOR distinct from mTORC1, or mTORC2 phosphorylates 4E-BP1. Ku-0063794 also suppressed cell growth and induced a G1-cell-cycle arrest. Our results indicate that Ku-0063794 will be useful in delineating the physiological roles of mTOR and may have utility in treatment of cancers in which this pathway is inappropriately activated.

scholarly journals Rag proteins regulate amino-acid-induced mTORC1 signalling

2009 ◽  
Vol 37 (1) ◽  
pp. 289-290 ◽  
Author(s):  
Yasemin Sancak ◽  
David M. Sabatini
Keyword(s):  
Amino Acid ◽  
Protein Kinase ◽  
Cell Growth ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Master Regulator ◽  
Growth And Survival ◽  
Field Identification ◽  
Rag Proteins ◽  
Cell Growth And Survival

The serum- and nutrient-sensitive protein kinase mTOR (mammalian target of rapamycin) is a master regulator of cell growth and survival. The mechanisms through which nutrients regulate mTOR have been one of the major unanswered questions in the mTOR field. Identification of the Rag (Ras-related GTPase) family of GTPases as mediators of amino acid signalling to mTOR is an important step towards our understanding of this mechanism.

Gambogic Acid Affects Ribosomal Occurrence in Glioma Cells by Downregulating the Phosphoinositide Kinase-3/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway

2020 ◽  
Vol 20 (6) ◽  
pp. 3361-3372 ◽  
Author(s):  
Guoxuan Luo ◽  
Shengqiang Jiang ◽  
Xu Zhang ◽  
Yunzhi Ling ◽  
Hengshan Luo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Protein Kinase B ◽  
Mammalian Target Of Rapamycin ◽  
Glioma Cells ◽  
Mtor Signaling ◽  
Target Of Rapamycin ◽  
Gambogic Acid ◽  
Mtor Signaling Pathway ◽  
Phosphoinositide Kinase

Gambogic acid (GA) is a natural compound with a polyprenylated xanthone structure that has antiinflammatory, antioxidant, and neuroprotective properties and acts as a chemopreventive agent. GA exhibits anti-tumor, antimicrobial, and anti-proliferative effects on cancer cells. In the current study, the effect of GA on phosphoinositide kinase-3 (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was examined in human U251 glioma cells. Cell viability and apoptosis were evaluated by MTT and Annexin V/PI Double Staining. The expressions of P38, AKT, and mTOR were evaluated by western blot and qRT-PCR, respectively. MagBeads Total RNA Extraction Kit was used to isolate cell tissue RNA. GA decreased the phosphorylation of P38, AKT, and mTOR. Inhibitors of PI3K (LY294002) enhanced the phosphorylation of P38, AKT, and mTOR. GA reduced the phosphorylation of ribosomal protein precursors (Pre) and upstream binding factor (UBF), and insulin-like growth factor I (IGF-1) further enhanced the cell proliferation and expression of Pre and UBF. These results suggested that downregulation of PI3K/AKT/mTOR signaling pathway may be an important mediator in GA-affected ribosomal occurrence in glioma cells.

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