title: Chalcoplatin, a dual-targeting and p53 activator-containing anticancer platinum(IV) prodrug with unique mode of action.
abstract: Complexation of cisplatin with a p53 activator as a single anticancer agent resulted in synergistically improved cytotoxicity in p53 wild-type but not p53 null human cancer cells. Mechanistic investigation was carried out on this dual-targeting Pt(IV) prodrug, chalcoplatin. The prodrug effectively entered cancer cells and arrested the cell cycle at the S and G2/M phases, distinctive of that from cisplatin. Chalcoplatin significantly induced p53 activation as well as the subsequent apoptosis pathways. This unique mode of action renders chalcoplatin remarkably cytotoxic and makes this compound among the first examples of a Pt(IV) prodrug that directly interacts with the downstream pathway after the formation of Pt-DNA lesions.
authors: Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong SAR. guangzhu@cityu.edu.hk.
authors: Lili
authors: L
authors: Ma
authors: Rong
authors: R
authors: Ma
authors: Yiping
authors: Y
authors: Wang
authors: Xiaoyue
authors: X
authors: Zhu
authors: Junliang
authors: J
authors: Zhang
authors: Hoi Ching
authors: HC
authors: Chan
authors: Xianfeng
authors: X
authors: Chen
authors: Wenjun
authors: W
authors: Zhang
authors: Sung-Kay
authors: SK
authors: Chiu
authors: Guangyu
authors: G
authors: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D047188:Chalcones / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000494:pharmacology*; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D009944:Organoplatinum Compounds; D011355:Prodrugs; D016159:Tumor Suppressor Protein p53; C000603498:chalcoplatin; D004247:DNA