title: Nedaplatin enhanced apoptotic effects of ABT-737 in human cancer cells via Mcl-1 inhibition.
abstract: Platinum compounds, such as cisplatin, carboplatin, oxaliplatin and nedaplatin, are widely used to treat a number of solid malignancies. Nedaplatin is a second-generation platinum complex, based on its pronounced anti-cancer activities against several solid tumors being equivalent to that of cisplatin, but with lower nephrotoxicity. In this context, the present study aimed to investigate the potential anti-cancer effect by combining nedaplatin with ABT-737. It was found that nedaplatin greatly increased ABT-737-mediated apoptosis in A549 and 95-D cells, accompanied by enhanced cleavage of poly(ADP-ribose) polymerase and caspase-3. In addition, this enhancement was also paralleled by cytochromecrelease and dissipation of mitochondrial membrane potential. Additional mechanistic investigations revealed that nedaplatin plus ABT-737 exerted a synergistic effect on cancer cells through their ability to accelerate the degradation of Mcl-1. The present study has revealed nedaplatin as a pertinent sensitizer to ABT-737, which opens up new avenues for this promising BH3-mimetic molecule in the clinic.
authors.affiliation: School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310006, P.R. China; Hangzhou Translational Medicine Research Center, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310006, P.R. China.
authors.forename: Yang-Ling
authors.initials: YL
authors.lastname: Li
authors.affiliation: The First Affiliated Hangzhou Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Weng
authors.affiliation: The First Affiliated Hangzhou Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Department of Pharmacy, Yongkang Hospital of Traditional Chinese Medicine, Yongkang, Zhejiang 321300, P.R. China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Li
authors.affiliation: School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Ming-Xian
authors.initials: MX
authors.lastname: Zhou
authors.affiliation: School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, Affiliated Hangzhou Hospital, Nanjing Medical University, Hangzhou, Zhejiang 310006, P.R. China; The First Affiliated Hangzhou Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China; Laboratory of Clinical Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
authors.forename: Neng-Ming
authors.initials: NM
authors.lastname: Lin
keywords: ABT-737; Mcl-1; cancer; combination; nedaplatin