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

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 signific...

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Main Authors:	Kang, Sokbom, Dong, Seung Myung, Kim, Boh-Ram, Park, Mi Sun, Trink, Barry, Byun, Hyun-Jung, Rho, Seung Bae
Format:	Online
Language:	English
Published:	Springer US 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413814/

id	pubmed-3413814
recordtype	oai_dc
spelling	pubmed-34138142012-08-23 Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical and endometrial cancer cells Kang, Sokbom Dong, Seung Myung Kim, Boh-Ram Park, Mi Sun Trink, Barry Byun, Hyun-Jung Rho, Seung Bae Original Paper 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. Springer US 2012-03-30 2012-09 /pmc/articles/PMC3413814/ /pubmed/22460505 http://dx.doi.org/10.1007/s10495-012-0717-2 Text en © The Author(s) 2012
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kang, Sokbom Dong, Seung Myung Kim, Boh-Ram Park, Mi Sun Trink, Barry Byun, Hyun-Jung Rho, Seung Bae
spellingShingle	Kang, Sokbom Dong, Seung Myung Kim, Boh-Ram Park, Mi Sun Trink, Barry Byun, Hyun-Jung Rho, Seung Bae Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical and endometrial cancer cells
author_facet	Kang, Sokbom Dong, Seung Myung Kim, Boh-Ram Park, Mi Sun Trink, Barry Byun, Hyun-Jung Rho, Seung Bae
author_sort	Kang, Sokbom
title	Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical and endometrial cancer cells
title_short	Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical and endometrial cancer cells
title_full	Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical and endometrial cancer cells
title_fullStr	Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical and endometrial cancer cells
title_full_unstemmed	Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical and endometrial cancer cells
title_sort	thioridazine induces apoptosis by targeting the pi3k/akt/mtor pathway in cervical and endometrial cancer cells
description	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.
publisher	Springer US
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413814/
_version_	1611548184587272192

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

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