5-Bromo-oxoisoaporphine platinum(II) complexes exhibit tumor cell cytotoxcicity via inhibition of telomerase activity and disruption of c-myc G-quadruplex DNA and mitochondrial functions

5-Bromo-oxoisoaporphine platinum(II) complexes exhibit tumor cell cytotoxcicity via inhibition of... 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 Δψ, 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Medicinal Chemistry Elsevier

5-Bromo-oxoisoaporphine platinum(II) complexes exhibit tumor cell cytotoxcicity via inhibition of telomerase activity and disruption of c-myc G-quadruplex DNA and mitochondrial functions

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Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Masson SAS
ISSN
0223-5234
eISSN
1768-3254
D.O.I.
10.1016/j.ejmech.2017.12.092
Publisher site
See Article on Publisher Site

Abstract

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 Δψ, 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.

Journal

European Journal of Medicinal ChemistryElsevier

Published: Feb 10, 2018

References

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