Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical and endometrial cancer cells

Sokbom Kang, Seung Myung Dong, Boh Ram Kim, Mi Sun Park, Barry Trink, Hyun Jung Byun, Seung Bae Rho

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)989-997
Number of pages9
Issue number9
StatePublished - Sep 2012
Externally publishedYes


  • Anti-cancer activity
  • Apoptosis
  • Cervical tumorigenesis
  • Thioridazine
  • mTOR signaling

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research


Dive into the research topics of 'Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical and endometrial cancer cells'. Together they form a unique fingerprint.

Cite this