Gambogenic acid induces apoptosis via upregulation of Noxa in oral squamous cell carcinoma

Gambogenic acid (GNA), a compound derived from the resin of Garcinia hanburyi, exhibits antitumor activities. However, the mechanism underlying the effect of GNA on oral squamous cell carcinoma (OSCC) remains poorly understood. The aim of this study was to evaluate the apoptotic action of GNA in the OSCC cell lines CAL-27 and SCC-15, and we found that GNA triggered apoptosis by upregulating Noxa protein expression. Mechanistically, our data determined that GNA induced reactive oxygen species (ROS) production, resulting in the activation of endoplasmic reticulum (ER) stress and eventually cell apoptosis. Blockade of ROS and ER stress attenuated GNA-induced Noxa upregulation and cell apoptosis. In vivo, GNA administration suppressed the growth of CAL-27 tumors in a murine xenograft model. Taken together, our results highlight GNA as a promising candidate for the treatment of OSCC.