Synthesis, characterization and anticancer activity in?vitro and in?vivo evaluation of an iridium (III) polypyridyl complex

摘要

Abstract An iridium (III) complex [Ir(ppy) 2 (BDPIP)]PF 6 ( Ir-1 ) was reported to show high anticancer activity and may be used as a potent anticancer drug. In the current study, we designed and synthesized a novel iridium (III) complex and evaluated its potential inhibitory effect on the cancer cell growth in?vitro and in?vivo. This complex was found to display high cytotoxic activity in?vitro and in?vivo against A549?cell with a low IC 50 value of 3.6?±?0.3?μM and inhibiting percentage of tumor growth is 63.84% compared with the control. The complex also exhibited potencies superior to that of cisplatin toward A549?cell in?vitro and in?vivo. Further studies revealed that the complex can induce apoptosis and autophagy, enhance the ROS level, cause a decrease in the mitochondrial membrane potential and inhibit the cell invasion. Our findings indicated that the complex induced apoptosis in A549 through mitochondria dysfunction and PI3K/AKT/mTOR signaling pathways. Graphical abstract A new iridium (III) complex [Ir(ppy) 2 (MDPIP)]PF 6 ( Ir-1 ) were synthesized and characterized. The anticancer activity of the complex was investigated by cytotoxic activity in?vitro and in?vivo, apoptosis, comet assay, ROS, mitochondrial membrane potential, autophagy, intracellular Ca 2+ levels, release of cytochrome c and PI3K/AKT/mTOR pathway. Display Omitted Highlights ? Cytotoxicity in?vitro and in?vivo of the complex against cancer cells was evaluated by MTT method. ? Apoptosis, ROS and mitochondrial membrane potential were assayed by fluorescent microscopy. ? The autophagy, intracellular Ca 2+ level, release of cytochrome c and cell invasion were studied. ? The cell cycle arrest and expression of Bcl-2 family proteins were investigated.