DN604: A platinum(II) drug candidate with classic SAR can induce apoptosis via suppressing CK2-mediated p-cdc25C subcellular localization in cancer cells

Journal Article · Thu Mar 15 04:00:00 EDT 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2018.01.031· OSTI ID:23082441

Chen, Feihong; Jin, Xiufeng; Zhao, Jian; Gou, Shaohua ^[1]

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1. Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189 (China)

Highlights: • DN604 exhibited stronger comparable cytotoxicity to cisplatin. • DN604 showed more potent in vivo antitumor activity than carboplatin. • DN604 resulted in negligible toxic effects as the same effect as cisplatin in vivo. • DN604 could suppress CK2-induced p-cdc25C activation and subcellular localization. DN604, a carboplatin analogue with a functional dicarboxylato ligand, was deeply investigated to explore its ability to induce apoptosis as well as its antitumor mechanism of action. Both in vitro and in vivo assays indicated that DN604 could effectively inhibit cell viability of SGC-7901 gastric cancer cells and exhibited stronger antitumor activity than carboplatin and comparable activity to cisplatin. Significantly in contrast to cisplatin, DN604 resulted in negligible toxic effects in vivo with the same tumor growth inhibition effect as cisplatin. The mechanism study indicated that DN604 inhibited CK2-phosphorylated cdc25C activation to decrease p-cdc25C subcellular localization, leading to the inactivation of cdc2/Cyclin B and G2/M cell cycle arrest and apoptosis in SGC-7901 cancer cells. Our research revealed for the first time that the dicarboxylato ligand containing a suitable functional moiety as the leaving group in the platinum(II) complex can effectively induce cell cycle arrest and apoptosis via inhibiting key checkpoint proteins.

• OSTI ID: 23082441
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 364; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL CYCLE
IN VITRO
IN VIVO
NEOPLASMS
PLATINUM
PROTEINS
TOXICITY