Two novel silver(I) phenanthroline derivative complexes induce G2/M phase cycle arrest and apoptosis of MDA-MB-231 cancer cells by multiple mechanisms

Two novel silver(I) phenanthroline derivative complexes (P-235 and P-239) have been synthesized and characterized by IR, HPLC-MS, and (HNMR)-H-1. The cytotoxicity of two complexes exhibited significant cytotoxicity against human breast cancer (MDA-MB-231) cell line (IC50 = 0.48 +/- 0.01 and 0.12 +/- 0.01 mu M) and less toxicity than cisplatin by MTT assays. Furthermore, anticancer mechanistic studies showed that P-235 and P-239 induced G2/M phase cell cycle arrest to inhibit the growth of MDA-MB-231 cells. Flow cytometry analysis showed that MDA-MB-231 cells could be significantly induced to undergo apoptosis by P-235 and P-239. And P-235- and P-239-induced apoptosis was linked with reactive oxygen species (ROS) production. Further study revealed that P-235 and P-239 cause mitochondrial membrane potential depolarization and destroy mitochondrial membrane potential.