LY294002 induces p53-dependent apoptosis of SGC7901 gastric cancer cells.

Abstract

AIM:

To study the effects of LY294002, an inhibitor of class I phosphatidylinositol 3-kinase (PI3K), on proliferation and apoptosis of SGC7901 gastric cancer cells.

METHODS:

The MTT assay was used to determine the cytotoxic effects of LY294002. Cell cycle distribution was analyzed using flow cytometry and apoptosis was assessed using flow cytometry analysis after staining DNA with propidium iodide. Mitochondrial membrane potential was measured using the fluorescent probe JC-1. Expression of p53 and PUMA was determined using real-time RT-PCR and Western blotting analysis.

RESULTS:

The viability of SGC7901 cells was significantly reduced by LY294002 treatment. Expression of p53 and PUMA was induced, and mitochondrial membrane potential collapsed after treatment with LY294002. LY294002 induced apoptotic cell death.

CONCLUSION:

Activation of the p53 pathway is involved in LY294002-induced SGC7901 cell death.

• Authors: Chun-gen Xing, Bao-song Zhu, Hui-hui Liu, Fang Lin, Hui-hua Yao, Zhong-qin Liang, Zheng-hong Qin
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 29 Issue 4 Pg. 489-98 (Apr 2008) ISSN: 1745-7254 [Electronic] United States
• PMID: 18358096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzimidazoles
• Carbocyanines
• Chromones
• Enzyme Inhibitors
• Fluorescent Dyes
• Formazans
• Morpholines
• Phosphoinositide-3 Kinase Inhibitors
• Tetrazolium Salts
• Tumor Suppressor Protein p53
• 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine
• MTT formazan
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one

Topics

• Apoptosis (drug effects)
• Benzimidazoles (metabolism)
• Carbocyanines (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chromones (pharmacology)
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (pharmacology)
• Fluorescent Dyes (metabolism)
• Formazans (metabolism)
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Morpholines (pharmacology)
• Phosphoinositide-3 Kinase Inhibitors
• Stomach Neoplasms (metabolism, pathology)
• Tetrazolium Salts (metabolism)
• Time Factors
• Tumor Suppressor Protein p53 (metabolism)