Implications of hydrogen sulfide in colorectal cancer: Mechanistic insights and diagnostic and therapeutic strategies

Hanchao Lin; Yixin Yu; Le Zhu; Nannan Lai; Luming Zhang; Yu Guo; Xinxin Lin; Dongqin Yang; Ning Ren; Zhiling Zhu; Qiongzhu Dong

doi:10.1016/j.redox.2023.102601

Implications of hydrogen sulfide in colorectal cancer: Mechanistic insights and diagnostic and therapeutic strategies

Redox Biol. 2023 Feb:59:102601. doi: 10.1016/j.redox.2023.102601. Epub 2023 Jan 7.

Authors

Hanchao Lin¹, Yixin Yu², Le Zhu³, Nannan Lai⁴, Luming Zhang⁴, Yu Guo³, Xinxin Lin⁴, Dongqin Yang⁵, Ning Ren⁶, Zhiling Zhu⁷, Qiongzhu Dong⁸

Affiliations

¹ Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission, Minhang Hospital, Fudan University, China; Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, China.
² College of Materials Science and Engineering, Qingdao University of Science and Technology, China.
³ Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, China.
⁴ Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission, Minhang Hospital, Fudan University, China.
⁵ Department of Digestive Diseases, Huashan Hospital, Fudan University, China. Electronic address: kobesakura@fudan.edu.cn.
⁶ Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission, Minhang Hospital, Fudan University, China; Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, And Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, China. Electronic address: ren.ning@zs-hospital.sh.cn.
⁷ College of Materials Science and Engineering, Qingdao University of Science and Technology, China. Electronic address: zlzhu@qust.edu.cn.
⁸ Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission, Minhang Hospital, Fudan University, China. Electronic address: qzhdong@fudan.edu.cn.

Abstract

Hydrogen sulfide (H₂S) is an important signaling molecule in colorectal cancer (CRC). It is produced in the colon by the catalytic synthesis of the colonocytes' enzymatic systems and the release of intestinal microbes, and is oxidatively metabolized in the colonocytes' mitochondria. Both endogenous H₂S in colonic epithelial cells and exogenous H₂S in intestinal lumen contribute to the onset and progression of CRC. The up-regulation of endogenous synthetases is thought to be the cause of the elevated H₂S levels in CRC cells. Different diagnostic probes and combination therapies, as well as tumor treatment approaches through H₂S modulation, have been developed in recent years and have become active area of investigation for the diagnosis and treatment of CRC. In this review, we focus on the specific mechanisms of H₂S production and oxidative metabolism as well as the function of H₂S in the occurrence, progression, diagnosis, and treatment of CRC. We also discuss the present challenges and provide insights into the future research of this burgeoning field.

Keywords: Cancer therapy; Colorectal cancer; Colorectal carcinogenesis; Diagnosis; Hydrogen sulfide; Sulfur metabolism.

Publication types

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

MeSH terms

Colorectal Neoplasms* / diagnosis
Colorectal Neoplasms* / drug therapy
Humans
Hydrogen Sulfide* / metabolism
Mitochondria / metabolism

Substances

Hydrogen Sulfide