Capsaicin,a Spicy Component of Hot Pepper,Induces Apoptosis by Activation of the Peroxisome Proliferator-Activated Receptor γ in HT-29 Human Colon Cancer Cells

Abstract

Capsaicin (N-vanillyl-8-methyl-α-nonenamide), a spicy component of hot pepper, is a homovanillic acid derivative that preferentially induces certain cancer cells to undergo apoptosis and has a putative role in cancer chemoprevention. Peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, is a ligand-dependent transcription factor. PAPRγ activation results in growth arrest and/or apoptosis in a variety of cancer cells. In the present study, we investigated the potential of capsaicin to induce apoptotic cell death in human colon cancer cells and the association of PPARγ in the capsaicin action. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. PPARγ and vanilloid receptor type 1 (VR-1) expressions at the protein or mRNA levels were detected by western blot analysis and reverse transcription–polymerase chain reaction. Apoptotic cell death was determined by DNA fragmentation and quantified by enzyme-linked immunosorbent assay. HT-29 human colon cancer cells expressed PPARγ and VR-1. Treatment with capsaicin or the PPARγ ligand troglitazone induced apoptotic cell death in a dose-dependent manner in HT-29 human colon cancer cells. Capsaicin-induced cell death was completely blocked by bisphenol A diglycidyl ether, a specific PPARγ antagonist. Capsazepine, a specific antagonist for vanilloid receptor, did not inhibit capsaicin-induced apoptosis. Our data suggest that capsaicin-induced apoptotic cell death in HT-29 human colon cancer cells could be associated with the PPARγ pathway without the involvement of the vanilloid receptor. Capsaicin may have a beneficial effect for the treatment of colon cancer.