Carbon monoxide (CO)/heme oxygenase (HO)-1 in gastrointestinal tumors pathophysiology and pharmacology - possible anti- and pro-cancer activities

Biochem Pharmacol. 2022 Jul:201:115058. doi: 10.1016/j.bcp.2022.115058. Epub 2022 Apr 28.

Abstract

Gastrointestinal (GI) tract cancers pose a significant pharmacological challenge for researchers in terms of the discovery of molecular agents and the development of targeted therapies. Although many ongoing clinical trials have brought new perspectives, there is still a lack of successful long-term treatment. Several novel pharmacological and molecular agents are being studied in the prevention and treatment of GI cancers. On the other hand, pharmacological tools designed to release an endogenous gaseous mediator, carbon monoxide (CO), were shown to prevent the gastric mucosa against various types of injuries and exert therapeutic properties in the treatment of GI pathologies. In this review, we summarized the current evidence on the role of CO and heme oxygenase 1 (HO-1) as a CO producing enzyme in the pathophysiology of GI tumors. We focused on a beneficial role of HO-1 and CO in biological systems and common pathological conditions. We further discussed the complex and ambiguous function of the HO-1/CO pathway in cancer cells with a special emphasis on molecular and cellular pro-cancerous and anti-cancer mechanisms. We also focused on the role that HO-1/CO plays in GI cancers, especially within upper parts such as esophagus or stomach.

Keywords: Carbon monoxide; Carbon monoxide-prodrugs; Colorectal cancer; Esophageal cancer; Gastric cancer; Heme oxygenase.

Publication types

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

MeSH terms

  • Carbon Monoxide / metabolism
  • Carbon Monoxide / pharmacology
  • Gastric Mucosa / metabolism
  • Gastrointestinal Diseases* / drug therapy
  • Gastrointestinal Neoplasms* / drug therapy
  • Gastrointestinal Neoplasms* / metabolism
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase-1 / metabolism
  • Humans

Substances

  • Carbon Monoxide
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1