期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 145, 期 -, 页码 360-369出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2017.12.092
关键词
5-bromo-oxoisoaporphine; Platinum(II) complexes; Cell apoptosis; Telomerase activity; Antitumor activity
资金
- National Natural Science Foundation of China [81473102, 21431001]
- Yulin Normal University [G2017009]
- Natural Science Foundation of Guangxi Province [2012GXNSFDA053005]
- BAGUI Scholar program of Guangxi Province of China
- [IRT_16R15]
- [CMEMR2012-A22]
Two platinum(II) complexes [Pt(L)(DMSO)Cl] (1) and [Pt(L)(pn)]Cl (2) with 5-bromo-oxoisoaporphine (H-L) were synthesized. We found that the two new platinum(II) complexes were more selective for Hep-G2 tumor cells than for normal cells (HL-7702, WI-38 and L-o2 cell lines). 5-Bromine-oxoisoaporphine platinum(II) complex 2 was a telomerase inhibitor targeting c-myc G4, and it triggered Hep-G2 cell apoptosis more potently than complex 1. Moreover, they induced cell apoptosis via disruption of mitochondrial functions. Significantly increased ROS level, loss of Delta psi, decrease of bcl-2 level, and increase of some of the mitochondria-initiated apoptosis protein levels (including bax, Cyt C, caspase-3, caspase-9, and apaf-1) were observed in Hep-G2 cells. In brief, complexes 1 and 2 triggered Hep-G2 cell apoptosis mainly through inhibiting telomerase activity by interacting with c-myc promoter elements and disruption of mitochondrial pathway. Our results also showed the effects of second ligands on the in vitro antitumor activity in the order of pn > Cl and DMSO. (C) 2018 Elsevier Masson SAS. All rights reserved.
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