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  3. A new gold(I) phosphine complex induces apoptosis in prostate cancer cells by increasing reactive oxygen species

A new gold(I) phosphine complex induces apoptosis in prostate cancer cells by increasing reactive oxygen species

  • Mol Cell Biochem. 2024 May 24. doi: 10.1007/s11010-024-05035-8.
Yuan Wang 1 2,  Haokun Yuan 3,  Ruiqin Fang 4,  Junzhu Lu 3,  Jiaqi Duo 3,  Ge Li 3,  Wei-Jia Wang 5 6
Affiliations

Affiliations

  • 1 The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, School of Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China. wangyuan_med@uestc.edu.cn.
  • 2 The School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. wangyuan_med@uestc.edu.cn.
  • 3 The School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
  • 4 The School of Life Science, University of Electronic Science and Technology of China, Chengdu, China.
  • 5 The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, School of Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China. wangwj@xmu.edu.cn.
  • 6 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China. wangwj@xmu.edu.cn.
PMID: 38782835 DOI: 10.1007/s11010-024-05035-8
Abstract

Thioredoxin reductase (TrxR) is a pivotal regulator of redox homeostasis. It is frequently overexpressed in various Cancer cells, including prostate Cancer, making it a promising target for the development of anti-cancer drugs. In this study, we screened a series of newly designed complexes of gold(I) phosphine. Specifically, Compound 5 exhibited the highest cytotoxicity against prostate Cancer cells and demonstrated stronger antitumor effects than commonly used drugs, such as cisplatin and auranofin. Importantly, our mechanistic study revealed that Compound 5 effectively inhibits the TrxR system in vitro. Additionally, Compound 5 promoted intracellular accumulation of Reactive Oxygen Species (ROS), leading to mitochondrial dysfunction and irreversible Apoptosis in prostate Cancer cells. Our in vivo xenograft study further demonstrated that Compound 5 has excellent antitumor activity against prostate Cancer cells, but does not cause severe side effects. These findings provide a promising lead Compound for the development of novel antitumor agents targeting prostate Cancer and offer a valuable tool for investigating biological pathways involving TrxR and ROS modulation.

Keywords

Apoptosis; Gold(I) complex; Prostate cancer; Reactive oxygen species; TrxR.

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