Cyclometalated ruthenium (II) complexes induced HeLa cell apoptosis through intracellular reductive injury

Xufeng Zhu; Qiang Sun; Xinhua Guo; Chunmei Liang; Yao Zhang; Wenyong Huang; Wenliang Pei; Zunnan Huang; Lanmei Chen; Jincan Chen

doi:10.1016/j.jinorgbio.2023.112333

Cyclometalated ruthenium (II) complexes induced HeLa cell apoptosis through intracellular reductive injury

J Inorg Biochem. 2023 Oct:247:112333. doi: 10.1016/j.jinorgbio.2023.112333. Epub 2023 Jul 15.

Authors

Xufeng Zhu¹, Qiang Sun², Xinhua Guo², Chunmei Liang³, Yao Zhang³, Wenyong Huang³, Wenliang Pei³, Zunnan Huang⁴, Lanmei Chen³, Jincan Chen⁵

Affiliations

¹ Guangdong Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Zhanjiang, Guangdong 524023, China; The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, Guangdong 524023, China.
² Guangdong Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Zhanjiang, Guangdong 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, Guangdong 524023, China.
³ Guangdong Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
⁴ Guangdong Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Zhanjiang, Guangdong 524023, China; Key Laboratory of Computer-Aided Drug Design of Dongguan City, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.
⁵ The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, Guangdong 524023, China; Key Laboratory of Computer-Aided Drug Design of Dongguan City, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China. Electronic address: jincanchen@126.com.

PMID: 37480763
DOI: 10.1016/j.jinorgbio.2023.112333

Abstract

The main challenge of cancer chemotherapy is the resistance of tumor cells to oxidative damage. Herein, we proposed a novel antitumor strategy: cyclic metal‑ruthenium (Ru) complexes mediate reductive damage to kill tumor cells. We designed and synthesized Ru(II) complexes with β-carboline as ligands: [Ru (phen)₂(NO₂-Ph-βC)](PF₆) (RuβC-7) and [Ru(phen)₂(1-Ph-βC)](PF₆) (RuβC-8). In vitro experimental results showed that RuβC-7 and RuβC-8 can inhibit cell proliferation, promote mitochondrial abnormalities, and induce DNA damage. Interestingly, RuβC-7 with SOD activity could reduce intracellular reactive oxygen species (ROS) levels, while RuβC-8 has the opposite effect. Accordingly, this study identified the reductive damage mechanism of tumor apoptosis, and may provide a new ideas for the design of novel metal complexes.

Keywords: Antitumor; ROS; Reductive damage; Ru(II) complexes; SOD activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Cell Proliferation
Coordination Complexes* / pharmacology
HeLa Cells
Humans
Ruthenium* / pharmacology

Substances

Ruthenium
Coordination Complexes