Abstract

Troglitazone, originally approved by the Food and Drug Administration for the management of type II diabetes, was later withdrawn due to its severe hepatotoxic effects. In an effort to repurpose Troglitazone, we investigated its potential antitumor effects on FaDu human hypopharyngeal carcinoma cells. Our study found that Troglitazone induced cell cycle arrest at the G2/M phase, which was accompanied by a reduction in key cyclins and cyclin-dependent kinase regulators. Simultaneously, Troglitazone upregulated negative regulators such as p21CIP1/WAF1 and p27KIP1. Furthermore, Troglitazone activated key apoptotic caspases, leading to the cleavage of poly (ADP-ribose) polymerase. These apoptotic responses were mediated through the intrinsic pathway, involving the regulation of both anti-apoptotic and pro-apoptotic factors. Notably, Troglitazone-induced apoptosis was linked to a marked increase in the expr ession of peroxisome proliferator-activated receptor gamma, and this effect was partially reversed by GW9662, a peroxisome proliferator-activated receptor gamma antagonist. In conclusion, our findings suggest that Troglitazone exerts its antitumor effects through peroxisome proliferator-activated receptor gamma activation, making it a promising candidate for repurposing as a therapeutic agent for human hypo pharyngeal car cinoma.