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Dihydroartemisinin potentiates the anticancer effect of cisplatin via mTOR inhibition in cisplatin-resistant ovarian cancer cells: involvement of apoptosis and autophagy

Feng, Xue, Li, Ling, Jiang, Hong, Jiang, Keping, Jin, Ye, Zheng, Jianhua (2014) Dihydroartemisinin potentiates the anticancer effect of cisplatin via mTOR inhibition in cisplatin-resistant ovarian cancer cells: involvement of apoptosis and autophagy. Biochemical and biophysical research communications, 444 (3). pp. 376-381. ISSN 0006-291X. E-ISSN 1090-2104. (doi:10.1016/j.bbrc.2014.01.053) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1016/j.bbrc.2014.01.053

Abstract

Dihydroartemisinin (DHA) exhibits anticancer activity in tumor cells but its mechanism of action is unclear. Cisplatin (DDP) is currently the best known chemotherapeutic available for ovarian cancer. However, tumors return de novo with acquired resistance over time. Mammalian target of rapamycin (mTOR) is an important kinase that regulates cell apoptosis and autophagy, and its dysregulation has been observed in chemoresistant human cancers. Here, we show that compared with control ovarian cancer cells (SKOV3), mTOR phosphorylation was abnormally activated in cisplatin-resistant ovarian cancer cells (SKOV3/DDP) following cisplatin monotherapy. Treatment with cisplatin combined with DHA could enhance cisplatin-induced proliferation inhibition in SKOV3/DDP cells. This mechanism is at least partially due to DHA deactivation of mTOR kinase and promotion of apoptosis. Although autophagy was also induced by DHA, the reduced cell death was not found by suppressing autophagic flux by Bafilomycin A1 (BAF). Taken together, we conclude that inhibition of cisplatin-induced mTOR activation is one of the main mechanisms by which DHA dramatically promotes its anticancer effect in cisplatin-resistant ovarian cancer cells.

Item Type: Article
DOI/Identification number: 10.1016/j.bbrc.2014.01.053
Uncontrolled keywords: Dihydroartemisinin; Cisplatin; Apoptosis; Autophagy; mTOR; Ovarian cancer
Subjects: Q Science
R Medicine
Divisions: Faculties > Sciences > School of Computing > Computing Education Group
Faculties > Sciences > School of Computing > Data Science
Depositing User: Caroline Li
Date Deposited: 17 Jul 2015 16:14 UTC
Last Modified: 29 May 2019 14:52 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/49593 (The current URI for this page, for reference purposes)
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