TY - JOUR
T1 - Gambogenic acid induces apoptosis via upregulation of Noxa in oral squamous cell carcinoma
AU - CHENG, Xinran
AU - FENG, Mengyuan
AU - ZHANG, Anjie
AU - GUO, Jian
AU - GONG, Yunlai
AU - HU, Xiaohui
AU - HAN, Quanbin
AU - LI, Shengbao
AU - YU, Xianjun
N1 - This work was supported by the Projects of International Cooperation and Exchanges (No. G2022027012L), the Natural Science Foundation of Hubei Provincial Department of Education (No. T2022021), the Advantages Discipline Group (Medicine) Project in Higher Education of Hubei Province (2021-2025) (Nos. 2024XKQY26 and 2023BMXKQY2), the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research of Hubei University of Medicine (No. WDCM2023007), the Innovative Research Program for Graduates of Hubei University of Medicine (No. YC2022033,YC2024003).
Publisher Copyright:
© 2024 China Pharmaceutical University
PY - 2024/7
Y1 - 2024/7
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Gambogenic acid
KW - Noxa
KW - Oral squamous cell carcinoma
KW - ROS/ER stress
UR - http://www.scopus.com/inward/record.url?scp=85199298823&partnerID=8YFLogxK
UR - https://www.sciencedirect.com/science/article/pii/S1875536424605789?via%3Dihub
U2 - 10.1016/S1875-5364(24)60578-9
DO - 10.1016/S1875-5364(24)60578-9
M3 - Journal article
C2 - 39059832
AN - SCOPUS:85199298823
SN - 2095-6975
VL - 22
SP - 632
EP - 642
JO - Chinese Journal of Natural Medicines
JF - Chinese Journal of Natural Medicines
IS - 7
ER -
