Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic Pathway

Jincan Chen; Jie Wang; Yuanyuan Deng; Tao Wang; Tifang Miao; Chengpeng Li; Xianhong Cai; Ying Liu; Justin Henri; Lanmei Chen

doi:10.1155/2020/8890950

Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic Pathway

Bioinorg Chem Appl. 2020 Aug 17:2020:8890950. doi: 10.1155/2020/8890950. eCollection 2020.

Authors

Jincan Chen¹, Jie Wang¹, Yuanyuan Deng¹, Tao Wang^{2

3}, Tifang Miao⁴, Chengpeng Li⁵, Xianhong Cai¹, Ying Liu¹, Justin Henri⁶, Lanmei Chen¹

Affiliations

¹ Guangdong Key Laboratory for Research and Development of Nature Drugs, Marine Biomedical Research Institute, School of Pharmacy, Guangdong Medical University, Zhanjiang 524023, China.
² School of Nursing, Zhengzhou University, Zhengzhou 450001, China.
³ Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth 6150, Australia.
⁴ School of Chemistry and Materials Science, Huaibei Normal University, Huaibei 235000, China.
⁵ The Public Service Platform of South China Sea for R&D Marine Biomedicine Resources, Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China.
⁶ School of Medicine Deakin University, Geelong, Victoria 3128, Australia.

Abstract

Two new Ru(II) complexes containing O, O-chelated ligands, Ru(dip)₂(SA) (Ru-1) and Ru(dmp)₂(SA) (Ru-2) (dip = 4,7-diphenyl-1,10-phenanthroline; dmp = 2,9-dimethyl-1,10-phenanthroline; SA = salicylate) were synthesized to evaluate their cytotoxicity in vitro. These complexes were found to exhibit moderate antitumor activity to different types of human cancers, including A549 (human lung carcinoma), MCF-7 (breast cancer), HeLa (human cervical cancer), and HepG2 (human hepatocellular carcinoma) cell lines, but displayed low toxicity to human normal cell lines BEAS-2B (immortalized human bronchial epithelial cells) when compared with that of cisplatin. Further studies revealed that these complexes could induce apoptosis in A549 cells, including activating caspase family proteins and poly (ADP-ribose) polymerase (PARP), reducing Bcl-2/Bax and Bcl-xl/Bad ratio, enhancing cellular reactive oxygen species (ROS) accumulation, triggering DNA damage, decreasing mitochondrial membrane potential (MMP), and leading cytochrome c release from mitochondria. Notably, complex Ru-1 showed low toxicity to developing zebrafish embryos. The obtained results suggest that these new synthetic complexes have the potential to be developed as low-toxicity agents for lung cancer treatment.