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Short-Chain Fatty Acids as Therapeutic Agents in Colon Malignancies

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Colon Cancer Diagnosis and Therapy

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.

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Abbreviations

AML:

Acute myeloid leukaemia

AT:

Acetate

BT:

Butyrate

CDK:

Cyclin-dependent kinase

CKIs:

Cyclin-dependent kinase inhibitors

CRC:

Colorectal cancer

DCA:

Dichloroacetate

DF:

Dietary fibres

EMP:

Embden-Meyerhof-Parnas pathway

FFAR:

Free fatty acid receptor

GI tract:

Gastrointestinal tract

GPCR/GPR:

G protein-coupled receptor

HAT:

Histone acetyltransferase

HDAC:

Histone deacetylase

HDACi:

HDAC inhibitors

IL:

Interleukin

IMC:

Intramucosal carcinoma

LPS:

Lipopolysaccharide

MAPK or MAP kinase:

Mitogen-activated protein kinase

MCA:

Multiple colorectal adenomas

MCP-1:

Monocyte chemoattractant protein-1

NaBT:

Sodium butyrate

NF-kβ:

Nuclear factor-kappa β

NOS:

Nitric oxide synthase

PDK-2:

Pyruvate dehydrogenase kinase isoform 2

PEP:

Phosphoenolpyruvate

PGC:

Peroxisome proliferator-activated receptor-gamma coactivator

PKS:

Polyketide synthase

PPARs:

Peroxisome proliferator-activated receptors

PT:

Propionate

RS:

Resistant starch

SCFAs:

Short-chain fatty acids

TNFα:

Tumour necrosis factor α

TSGs:

Tumour suppressor genes

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Author notes

  1. Arundhati Mehta and Vivek Kumar Soni contributed equally as first author, with all other contributors.

Authors and Affiliations

  1. Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India

    Arundhati Mehta, Vivek Kumar Soni, Yashwant Kumar Ratre, Rajat Pratap Singh, Dhananjay Shukla & Naveen Kumar Vishvakarma

  2. Uttar Pradesh-State AIDS Control Society (UPSACS), National AIDS Control Organization-Public Health foundation of India-Technical Support Unit (NACO-PHFI-TSU), Lucknow, Uttar Pradesh, India

    Rakesh Kumar Rai

  3. Department of Molecular and Cell Biology, Henry Welcome Building, University of Leicester, Leicester, UK

    Navaneet Chaturvedi

  4. School of Biochemical Engineering, Indian Institute of Technology-Banaras Hindu University (IIT-BHU), Varanasi, Uttar Pradesh, India

    Navaneet Chaturvedi

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  1. Arundhati Mehta
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Editors and Affiliations

  1. Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA

    Ganji Purnachandra Nagaraju

  2. Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, India

    Dhananjay Shukla

  3. Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, India

    Naveen Kumar Vishvakarma

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Mehta, A. et al. (2021). Short-Chain Fatty Acids as Therapeutic Agents in Colon Malignancies. In: Nagaraju, G.P., Shukla, D., Vishvakarma, N.K. (eds) Colon Cancer Diagnosis and Therapy. Springer, Cham. https://doi.org/10.1007/978-3-030-63369-1_10

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