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Gambogenic acid induces apoptosis via upregulation of Noxa in oral squamous cell carcinoma 认领 引用 被引量：3
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作者 CHENG Xinran FENG Mengyuan +6 位作者 ZHANG Anjie GUO Jian GONG Yunlai HU Xiaohui HAN Quanbin LI Shengbao YU Xianjun 《Chinese Journal of Natural Medicines》 SCIE CAS CSCD 2024年第7期632-642,共11页
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 larg... 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. 展开更多
关键词 Oral squamous cell carcinoma Gambogenic acid Apoptosis Noxa ROS/ER stress
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Gambogenic acid ameliorates inflammation by inhibiting HK1-mediated Warburg effect and NLRP3 inflammasome activation in sepsis 认领 引用 被引量：1
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作者 Huanhuan Pang Honglin Chen +18 位作者 Peng Chen Xu Wei Hongda Liu Xueling He Yang Yang Junzhe Zhang Dianfei Li Linlin Lou Wen Xie Chong Qiu Fei Xia Qiuyan Guo Shengnan Shen Qiaoli Shi Weiguang Li Guang Han Xijun Wang Jigang Wang Chengchao Xu 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2026年第1期337-351,共15页
Sepsis is a life-threatening disease caused by the dysregulated host immune response to infection, which eventually leads to multi-organ failure. Current therapeutic strategies rely heavily on antibiotics. However, co... Sepsis is a life-threatening disease caused by the dysregulated host immune response to infection, which eventually leads to multi-organ failure. Current therapeutic strategies rely heavily on antibiotics. However, conventional antimicrobial therapy often leads to antibiotic abuse and resistance. Therefore, it is of utmost importance to develop new agents for treating sepsis. Here, we demonstrated that gambogenic acid (GNA) not only restricted the release of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated macrophages but also attenuated the inflammatory response and organ damage in septic mice. By using the activity-based protein profiling (ABPP) strategy, we identified 30 potential target proteins of GNA. Among these potential targets, we found that GNA directly bound to the Cys684 residue of hexokinase 1 (HK1) and affected its enzyme activity and cellular localization. These findings were confirmed by the cellular thermal shift assay (CETSA), bio-layer interferometry (BLI), and single-site mutation experiments. Functionally, siHK1 alleviated the Warburg effect, suppressed the activation of NLRP3 inflammasome, and eventually suppressed the release of inflammatory cytokines. Taken together, our findings demonstrated that GNA could attenuate inflammation by alleviating HK1-mediated Warburg effect and NLRP3 inflammasome activation in sepsis and could serve as a novel therapeutic agent for sepsis and inflammatory disorders. 展开更多
关键词 Inflammation Activity-based protein profiling(ABPP) Target identification Chemical proteomics Gambogenic acid(GNA) Hexokinase 1(HK1) Warburg effect Sepsis
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