Short-chain fatty acids as therapeutic agents in colon malignancies

Abstract

Colon cancer has taken a large number of lives worldwide and stands among the few topmost killer malignancies. Although several approaches to combat the detrimental effects of neoplastic cells have been implemented in preclinical and clinical settings, these transformed cells display aggressive and recalcitrant behaviour during progression as well as treatment. Natural metabolites of microbial origin have recently attracted the biomedical investigators to owing to vast diversity and bioactivity. Short-chain fatty acids (SCFA) are products of fermentative metabolism of the microbiota of the gut. They contain fewer than six carbons and include butyrate, propionate, acetate, and lactate. SCFA are known for their ability to hinder the process of oncogenesis at the earliest and can serve as therapeutic agents. Apart from their metabolite nature, SCFA butyrate and propionate can stimulate cell surface receptors and alter the phenotypic behaviour of affected cells. Dedicated but ambiguous transporters for these SCFAs are known, and their cellular presence has a distinct consequence on metabolic modulation of normal as well as transformed cells. Further, SCFA can modulate the key enzymes governing the epigenetic state of cells. Targeted members of epigenetic machinery include, but not limited to, HDACs and HAT. SCFA has shown potential in the management of cancers of various etiological origins. Moreover, SCFA can potentiate the ability of standard anticancer drugs through modulation of chemo-resistant conduct of transformed cells. This book chapter discusses the potential of SCFAs in colon cancer treatment with their possible mechanisms. Understanding the impending role of SCFA as therapeutic moieties will assist in designing therapeutic strategies using SCFA. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2021. All rights reserved.