The Anticancer Potential of Peroxisome Proliferator‐Activated Receptor Antagonists

Abstract

The effects on cancer-cell proliferation and differentiation mediated by peroxisome proliferator-activated receptors (PPARs) have been widely studied, and pleiotropic outcomes in different cancer models and under different experimental conditions have been obtained. Interestingly, few studies report and little preclinical evidence supports the potential antitumor activity of PPAR antagonists. This review focuses on recent findings on the antitumor in vitro and in vivo effects observed for compounds able to inhibit the three PPAR subtypes in different tumor models, providing a rationale for the use of PPAR antagonists in the treatment of tumors expressing the corresponding receptors.

PPARβ/δ: Linking Metabolism to Regeneration

“…PPARβ/δ can be activated by endogenous ligands like polyunsaturated fatty acids and eicosanoid metabolites (e.g., prostacyclin and 15-hydroxyeicosatetraenoic acid (15-HETE)) as well as artificial agonists including GW501516, GW0742, L-165041, and carbacyclin [ 8 , 9 ]. In addition, the action of PPARβ/δ can be inhibited by several inverse agonists and antagonists [ 10 ]. Yet, there are currently neither agonistic nor antagonistic drugs clinically available [ 10 , 11 ].…”

“…In addition, the action of PPARβ/δ can be inhibited by several inverse agonists and antagonists [ 10 ]. Yet, there are currently neither agonistic nor antagonistic drugs clinically available [ 10 , 11 ].…”

PPAR Ligands Induce Antiviral Effects Targeting Perturbed Lipid Metabolism during SARS-CoV-2, HCV, and HCMV Infection

“…PPAR agonists, antagonists, and modulators represent important pharmacological tools to induce beneficial therapeutic effects in metabolic disorders, such as metabolic syndrome, obesity, diabetes, and others [ 53 , 54 , 55 , 56 ]. Recently, PPARs have been attracting a great deal of interest as targets in different cancers, thanks to their ability to induce important metabolic changes in tumors, and several PPAR ligands have been studied for their possible antitumor effects [ 57 , 58 , 59 , 60 ].…”

Sulfonimide and Amide Derivatives as Novel PPARα Antagonists: Synthesis, Antiproliferative Activity, and Docking Studies

“…Some tumors, including leukemia, prostate, ovarian, and renal cell carcinomas, are strongly dependent on FAO for survival and proliferation. 8 PPARα antagonists showed antitumor effects in different cancer cell lines, 9 as chronic lymphocytic leukemia, 10 renal cell carcinoma, 11 glioblastoma, 12 colorectal and pancreatic cancer, 13 and paraganglioma. 14,15 In the search for novel PPAR antagonists, in this work we describe an agonist−antagonist switching design.…”