甘珀酸通过上调 Noxa 诱导口腔鳞状细胞癌细胞凋亡

IF 4 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Chinese Journal of Natural Medicines Pub Date : 2024-07-01 DOI:10.1016/S1875-5364(24)60578-9
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引用次数: 0

摘要

甘比原酸(GNA)是一种生物活性化合物,提取自加纳藤的树脂,具有显著的抗肿瘤特性。然而,它在口腔鳞状细胞癌(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。结果表明,GNA通过上调促凋亡蛋白Noxa诱导细胞凋亡。机理研究发现,GNA 处理会导致活性氧(ROS)的产生,从而激活内质网(ER)应激,最终导致细胞凋亡。抑制 ROS 生成和 ER 应激途径可明显缓解 GNA 诱导的 Noxa 上调和随后的细胞凋亡。此外,使用小鼠异种移植模型进行的体内研究表明,服用 GNA 能有效抑制 CAL-27 肿瘤的生长。总之,这些研究结果凸显了 GNA 作为一种治疗剂治疗 OSCC 的潜力。
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Gambogenic acid induces apoptosis via upregulation of Noxa in oral squamous cell carcinoma

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.

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来源期刊
Chinese Journal of Natural Medicines
Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY
CiteScore
7.50
自引率
4.30%
发文量
2235
期刊介绍: The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.
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