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

Abstract

Gambogenic acid (GNA), a bioactive compound derived from the resin of Garcinia hanburyi, has demonstrated significant antitumor properties. However, its mechanisms of action in oral squamous cell carcinoma (OSCC) remain largely unclear. This study aimed to elucidate the apoptotic effects of GNA on OSCC cell lines CAL-27 and SCC-15. Our results indicated that GNA induced apoptosis by upregulating the pro-apoptotic protein Noxa. Mechanistic investigations revealed that GNA treatment led to the generation of reactive oxygen species (ROS), which activated endoplasmic reticulum (ER) stress, culminating in cell apoptosis. Inhibition of ROS production and ER stress pathways significantly mitigated GNA-induced Noxa upregulation and subsequent apoptosis. Furthermore, in vivo studies using a murine xenograft model demonstrated that GNA administration effectively inhibited the growth of CAL-27 tumors. Collectively, these findings underscore GNA’s potential as a therapeutic agent for the treatment of OSCC.

Keywords

Oral squamous cell carcinoma / Gambogenic acid / Apoptosis / Noxa / ROS/ER stress

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Funding

Projects of International Cooperation and Exchanges(G2022027012L)

Natural Science Foundation of Hubei Provincial Department of Education(T2022021)

Advantages Discipline Group (Medicine) Project in Higher Education of Hubei Province (2021-2025)(2024XKQY26)

Advantages Discipline Group (Medicine) Project in Higher Education of Hubei Province (2021-2025)(2023BMXKQY2)

Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research of Hubei University of Medicine(WDCM2023007)

Innovative Research Program for Graduates of Hubei University of Medicine(YC2022033)

Innovative Research Program for Graduates of Hubei University of Medicine(YC2024003)