title: A hybrid platinum drug dichloroacetate-platinum(II) overcomes cisplatin drug resistance through dual organelle targeting.
abstract: 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.
authors: 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.
authors: Yu
authors: Y
authors: Zhang
authors: Guannan
authors: G
authors: Guo
authors: Ben
authors: B
authors: Ma
authors: Rong
authors: R
authors: Du
authors: Haihua
authors: H
authors: Xiao
authors: Xiaoguang
authors: X
authors: Yang
authors: Wenliang
authors: W
authors: Li
authors: Ying
authors: Y
authors: Gao
authors: Yuxin
authors: Y
authors: Li
authors: Xiabin
authors: X
authors: Jing
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D062845:Chloroacetates / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D056831:Coordination Complexes / Q000494:pharmacology*; D018736:DNA Adducts / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010051:Ovarian Neoplasms
chemical_list: D000970:Antineoplastic Agents; D062845:Chloroacetates; D056831:Coordination Complexes; D018736:DNA Adducts; D009944:Organoplatinum Compounds; C000602568:diammine(dichloroacetato)platinum(II); D002945:Cisplatin