Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China; 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; Inflammation-Cancer Transformation and Wudang Chinese Medicine Research, Hubei Talent Introduction and Innovation Demonstration Base, Hubei University of Medicine, Shiyan 442000, China.
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; Inflammation-Cancer Transformation and Wudang Chinese Medicine Research, Hubei Talent Introduction and Innovation Demonstration Base, Hubei University of Medicine, Shiyan 442000, China.
Chin J Nat Med. 2024 Jul;22(7):632-642. doi: 10.1016/S1875-5364(24)60578-9.
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.
藤黄酸（GNA）是一种来源于藤黄树脂的生物活性化合物，已被证明具有显著的抗肿瘤特性。然而，其在口腔鳞状细胞癌（OSCC）中的作用机制在很大程度上仍不清楚。本研究旨在阐明 GNA 对 OSCC 细胞系 CAL-27 和 SCC-15 的凋亡作用。我们的结果表明，GNA 通过上调促凋亡蛋白 Noxa 诱导细胞凋亡。机制研究表明，GNA 处理导致活性氧（ROS）的产生，激活内质网（ER）应激，最终导致细胞凋亡。抑制 ROS 产生和 ER 应激途径可显著减轻 GNA 诱导的 Noxa 上调和随后的细胞凋亡。此外，利用小鼠异种移植模型的体内研究表明，GNA 给药可有效抑制 CAL-27 肿瘤的生长。总之，这些发现强调了 GNA 作为治疗 OSCC 的治疗剂的潜力。
