Thioridazine Induces Apoptosis by Targeting the PI3K/Akt/mTOR Pathway in Cervical and Endometrial Cancer Cells

Overview

Journal Apoptosis

Publisher Springer

Date 2012 Mar 31

PMID 22460505

Citations 66

Authors

Sokbom Kang

Seung Myung Dong

Boh-Ram Kim

Mi Sun Park

Barry Trink

Hyun-Jung Byun

Seung Bae Rho

Affiliations

Soon will be listed here.

Abstract

Recently, thioridazine (10-[2-(1-methyl-2-piperidyl) ethyl]-2-methylthiophenothiazine), a well-known anti-psychotic agent was found to have anti-cancer activity in cancer cells. However, the molecular mechanism of the agent in cellular signal pathways has not been well defined. Thioridazine significantly increased early- and late-stage apoptotic fraction in cervical and endometrial cancer cells, suggesting that suppression of cell growth by thioridazine was due to the induction of apoptosis. Cell cycle analysis indicated thioridazine induced the down-regulation of cyclin D1, cyclin A and CDK4, and the induction of p21 and p27, a cyclin-dependent kinase inhibitor. Additionally, we compared the influence of thioridazine with cisplatin used as a control, and similar patterns between the two drugs were observed in cervical and endometrial cancer cell lines. Furthermore, as expected, thioridazine successfully inhibited phosphorylation of Akt, phosphorylation of 4E-BP1 and phosphorylation of p70S6K, which is one of the best characterized targets of the mTOR complex cascade. These results suggest that thioridazine effectively suppresses tumor growth activity by targeting the PI3K/Akt/mTOR/p70S6K signaling pathway.

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