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Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2022; 28(28): 3535-3554
Published online Jul 28, 2022. doi: 10.3748/wjg.v28.i28.3535
Peroxisome proliferator-activated receptor gamma as a therapeutic target for hepatocellular carcinoma: Experimental and clinical scenarios
Swati Katoch, Vinesh Sharma, Vikram Patial
Swati Katoch, Vinesh Sharma, Vikram Patial, Division of Dietetics and Nutrition Technology, Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India
Swati Katoch, Vinesh Sharma, Vikram Patial, Academy of Scientific and Innovative Research, Ghaziabad 201002, UP, India
Author contributions: Katoch S and Sharma V wrote the manuscript and contributed equally to the manuscript; Patial V contributed to the conception of the study, manuscript writing and editing; All authors have read and approved the final manuscript.
Supported by CSIR, India, No. MLP0204.
Conflict-of-interest statement: The authors have no conflict of interests to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Vikram Patial, PhD, Senior Scientist, Division of Dietetics and Nutrition Technology, Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India. vikrampatial@ihbt.res.in
Received: January 17, 2022
Peer-review started: January 17, 2022
First decision: April 11, 2022
Revised: April 25, 2022
Accepted: June 24, 2022
Article in press: June 24, 2022
Published online: July 28, 2022
Abstract

Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Viral hepatitis is a significant risk factor for HCC, although metabolic syndrome and diabetes are more frequently associated with the HCC. With increasing prevalence, there is expected to be > 1 million cases annually by 2025. Therefore, there is an urgent need to establish potential therapeutic targets to cure this disease. Peroxisome-proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor that plays a crucial role in the patho-physiology of HCC. Many synthetic agonists of PPARγ suppress HCC in experimental studies and clinical trials. These synthetic agonists have shown promising results by inducing cell cycle arrest and apoptosis in HCC cells and preventing the invasion and metastasis of HCC. However, some synthetic agonists also pose severe side effects in addition to their therapeutic efficacy. Thus natural PPARγ agonists can be an alternative to exploit this potential target for HCC treatment. In this review, the regulatory role of PPARγ in the pathogenesis of HCC is elucidated. Furthermore, the experimental and clinical scenario of both synthetic and natural PPARγ agonists against HCC is discussed. Most of the available literature advocates PPARγ as a potential therapeutic target for the treatment of HCC.

Keywords: Anticancer, Hepatocellular carcinoma, Natural agonists, Peroxisome proliferator-activated receptor-γ, Thiazolidinediones

Core Tip: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Viral infections and metabolic syndrome are the major risk factors for HCC, and its incidence is expected to increase to > 1 million cases annually by 2025. The crucial role of peroxisome-proliferator-activated receptor gamma (PPARγ) in HCC pathophysiology makes it a potential therapeutic target. Along with synthetic agonists, natural PPARγ agonists provide alternative and safer options for HCC treatment; however, they need to be validated clinically. This review discusses the regulatory role of PPARγ in HCC pathogenesis and experimental and clinical scenarios of PPARγ agonists in HCC treatment.