Gallium Complex K6 Inhibits Colorectal Cancer by Increasing ROS Levels to Induce DNA Damage and Enhance Phosphatase and Tensin Homolog Activity

Overview

Journal MedComm (2020)

Specialty Health Services

Date 2024 Jul 25

PMID 39049965

Authors

Wei Li

Chuanyu Yang

Zhuo Cheng

Yuanyuan Wu

Sihan Zhou

Xiaowei Qi

Yi Zhang

Jinhui Hu

Mingjin Xie

Ceshi Chen

Affiliations

Soon will be listed here.

Abstract

Colorectal cancer (CRC) is one of the most common malignancies worldwide. In the clinical realm, platinum-based drugs hold an important role in the chemotherapy of CRC. Nonetheless, a multitude of patients, due to tumor protein 53 () gene mutations, experience the emergence of drug resistance. This phenomenon gravely impairs the effectiveness of therapy and long-term prognosis. Gallium, a metallic element akin to iron, has been reported that has the potential to be used to develop new metal anticancer drugs. In this study, we screened and established the gallium complex K6 as a potent antitumor agent in both in vitro and in vivo. K6 exhibited superior efficacy in impeding the growth, proliferation, and viability of CRC cells carrying mutations compared to oxaliplatin. Mechanistically, K6 escalated reactive oxygen species levels and led deoxyribonucleic acid (DNA) damage. Furthermore, K6 effectively suppressed the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB)/glycogen synthase kinase 3 beta (GSK3β) pathway, leading to the degradation of its downstream effectors myelocytomatosis (c-Myc) and Krueppel-like factor 5 (KLF5). Conversely, K6 diminished the protein expression of WW domain-containing protein 1 (WWP1) while activating phosphatase and tensin homolog (PTEN) through c-Myc degradation. This dual action further demonstrated the potential of K6 as a promising therapeutic compound for -mutated CRC.

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