MPT0G066, a novel anti-mitotic drug, induces JNK-independent mitotic arrest, JNK-mediated apoptosis, and potentiates antineoplastic effect of cisplatin in ovarian cancer

Han Li Huang, Min Wu Chao, Ya Chi Li, Li Hsun Chang, Chun-Han Chen, Mei Chuan Chen, Chun Chun Cheng, Jing Ping Liou, Che Ming Teng, Shiow Lin Pan

研究成果: 雜誌貢獻文章

7 引文 斯高帕斯(Scopus)

摘要

Developing new anticancer agents against ovarian cancer is an urgent medical need. MPT0G066, a novel synthetic arylsulfonamide compound, was shown to inhibit cell growth and decrease viability in human ovarian cancer cells. MPT0G066 induced arrest of the cell cycle at the multipolyploidy (MP) phase in SKOV3 and at the G2/M phase in A2780 cells, while increasing the proportion of cells in the subG1. Additionally, MPT0G066 induced c-Jun-NH2 terminal kinase (JNK) activation, influenced cell cycle regulatory and Bcl-2 family proteins, which triggered intrinsic apoptotic pathways through cleavage of caspase-3,-7,-9, and poly-(ADP-ribose) polymerase (PARP). Flow cytometry analysis of p-glycoprotein (p-gp) function showed that MPT0G066 was not a substrate of p-gp. Additionally, it was shown that MPT0G066 could decrease cell viability in multiple-drug-resistant human ovarian cancer cells. Furthermore, the combination of MPT0G066 and cisplatin presented a synergistic cytotoxic effect against ovarian cancer cell lines in vitro. MPT0G066 also significantly suppressed the growth of ovarian carcinoma and potentiated the antineoplastic effects of cisplatin in vivo. In conclusion, these findings indicate that MPT0G066 can be a potential anticancer agent against ovarian cancer that worthy of further development.
原文英語
文章編號31664
期刊Scientific Reports
6
DOIs
出版狀態已發佈 - 八月 16 2016

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