A hybrid drug dichloroacetate-platinum(II) [DCA-Pt(II)] was found to overcome cisplatin drug resistance of ovarian cancer through a dual targeting mode, which is different from the mode of action of the present platinum (Pt) drugs used in clinics. DCA-Pt(II) exhibited remarkable cytotoxicity against both cisplatin-sensitive (A2780) and cisplatin-resistant (A2780DDP) ovarian cancer cells. The Pt and Pt-DNA adduct content test showed that there was less Pt cellular uptake and fewer Pt-DNA adducts were present after DCA-Pt(II) treatment compared with treatment with cisplatin, carboplatin, and some other drugs. In the study, the effects of DCA-Pt(II) on the cell cycle and apoptosis were also investigated, which showed that DCA-Pt(II) induced G2/M phase arrest and mitochondria-mediated apoptosis in both sensitive and resistant cells lines. Interestingly, DCA-Pt(II) had much greater effects on mitochondria in A2780DDP cell lines than in A2780 cell lines.
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aNational Engineering Laboratory for Druggable Gene and Protein Screening
bJilin Province Key Laboratory on Chemistry and Biology of Natural Drugs in Changbai Mountain, School of Life Sciences, Northeast Normal University
cState Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences
dSchool of Chemistry & Environmental Engineering, Changchun University of Science and Technology, Changchun, China
* Yu Zhang and Guannan Guo contributed equally to the writing of this article.
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Correspondence to Wenliang Li, PhD, National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China Tel: +86 431 89165937; fax: +86 431 89165917; e-mail: email@example.com and Yuxin Li, PhD, Jilin Province Key Laboratory on Chemistry and Biology of Natural Drugs in Changbai Mountain, School of Life Sciences, Northeast Normal University, Changchun 130024, China Tel/fax:+86 431 89165926; e-mail: firstname.lastname@example.org
Received October 31, 2014
Accepted February 24, 2015