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

作　　者：CHENG Xinran FENG Mengyuan ZHANG Anjie GUO Jian GONG Yunlai HU Xiaohui HAN Quanbin LI Shengbao YU Xianjun 

机构地区：[1]Department of Gastroenterology,Taihe Hospital,Hubei University of Medicine,Shiyan 442000,China [2]Laboratory of Inflammation and Molecular Pharmacology,School of Basic Medical Sciences&Biomedical Research Institute,Hubei Key Laboratory of Wudang Local Chinese Medicine Research,School of Pharmacy,Hubei University of Medicine,Shiyan 442000,China [3]Inflammation-Cancer Transformation and Wudang Chinese Medicine Research,Hubei Talent Introduction and Innovation Demonstration Base,Hubei University of Medicine,Shiyan 442000,China [4]School of Chinese Medicine,Hong Kong Baptist University,Hong Kong 999077,China

出　　处：《Chinese Journal of Natural Medicines》2024年第7期632-642,共11页中国天然药物（英文版）

基　　金：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).

摘　　要：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.

关 键 词：Oral squamous cell carcinoma Gambogenic acid APOPTOSIS NOXA ROS/ER stress 

分 类 号：R965[医药卫生—药理学]