Class I phosphatidylinositol 3-kinase inhibitor LY294002 activates autophagy and induces apoptosis through p53 pathway in gastric cancer cell line SGC7901.

Abstract

We aimed to study the effects of LY294002, an inhibitor of class I phosphatidylinositol 3-kinase (PI3K), on proliferation, apoptosis, and autophagy in gastric cancer cell line SGC7901. In this study, we showed that LY294002 inhibited the viability of gastric cancer SGC7901 cells. We also showed that LY294002 increased the expression of microtubule-associated protein 1 light chain 3 (LC3), and increased monodansylcadaverine (MDC)-labeled vesicles. LY294002 activated autophagy by activating p53 and caspase-3, and induced apoptosis by up-regulating p53 and p53-up-regulated modulator of apoptosis (PUMA). Therefore, LY294002 might induce cytotoxicity in SGC7901 cells through activation of p53 and the downstream point PUMA. These findings suggest that inhibition of the class I PI3K signaling pathway is a potential strategy for managing gastric cancers.

• Authors: Chungen Xing, Baosong Zhu, Huihui Liu, Huihua Yao, Lifeng Zhang
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 40 Issue 3 Pg. 194-201 (Mar 2008) ISSN: 1745-7270 [Electronic] China
• PMID: 18330473 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromones
• Morpholines
• Phosphoinositide-3 Kinase Inhibitors
• TP53 protein, human
• Tumor Suppressor Protein p53
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one

Topics

• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Cell Line, Tumor
• Chromones (administration & dosage)
• Dose-Response Relationship, Drug
• Humans
• Mice
• Morpholines (administration & dosage)
• Phosphoinositide-3 Kinase Inhibitors
• Signal Transduction (drug effects)
• Stomach Neoplasms (metabolism, pathology)
• Tumor Suppressor Protein p53 (metabolism)