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

Abstract

Two novel silver(I) phenanthroline derivative complexes (P‐235 and P‐239) have been synthesized and characterized by IR, HPLC‐MS, and 1HNMR. 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 μM) 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.