Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
Am J Chin Med. 2022;50(6):1663-1679. doi: 10.1142/S0192415X22500707. Epub 2022 Jul 2.
Gambogic acid (GA), a natural and bioactive compound from the gamboge resin, has been reported to exhibit many oncostatic activities against several types of malignancies. However, its effects on the progression of oral squamous cell carcinoma (OSCC) remain largely unexplored. To fill this gap, we investigated the anticancer role of GA and molecular mechanisms underlying GA's actions in combating oral cancer. We found that GA negatively regulated the viability of OSCC cells, involving induction of the sub-G1 phase and cell apoptosis. In addition, a specific signature of apoptotic proteome, such as upregulation of heme oxygenase-1 (HO-1) and activation of caspase cascades, was identified in GA-treated OSCC. Moreover, such induction of HO-1 expression and caspase cleavage by GA was significantly diminished through the pharmacological inhibition of p38 kinase. In conclusion, these results demonstrate that GA promotes cell apoptosis in OSCC, accompanied with the activation of a p38-dependent apoptotic pathway. Our findings provide potential avenues for the use of GA with high safety and therapeutic implications in restraining oral cancer.
藤黄酸（GA）是藤黄树脂中的一种天然生物活性化合物，据报道具有多种抗肿瘤活性，可抑制多种恶性肿瘤。然而，其对口腔鳞状细胞癌（OSCC）进展的影响在很大程度上仍未得到探索。为了填补这一空白，我们研究了 GA 的抗癌作用及其在对抗口腔癌中的作用机制。我们发现 GA 可负向调节 OSCC 细胞的活力，涉及诱导亚 G1 期和细胞凋亡。此外，GA 处理后的 OSCC 中还鉴定到了凋亡蛋白组的特定特征，如血红素加氧酶-1（HO-1）的上调和 caspase 级联的激活。此外，GA 诱导的 HO-1 表达和 caspase 切割通过 p38 激酶的药理学抑制明显减少。总之，这些结果表明 GA 可促进 OSCC 细胞凋亡，并伴有 p38 依赖性凋亡途径的激活。我们的研究结果为使用 GA 提供了潜在途径，GA 具有高安全性和治疗意义，可抑制口腔癌。
