Lee Jihjong, Huang Ming-Shyan, Yang I-Chi, Lai Tsung-Ching, Wang Jui-Ling, Pang Victor Fei, Hsiao Michael, Kuo Mark Y P
Graduate Institute of Veterinary Medicine, College of Biological Resources and Agriculture, National Taiwan University, Taipei, Taiwan.
Biochem Biophys Res Commun. 2008 Jun 20;371(1):33-8. doi: 10.1016/j.bbrc.2008.03.149. Epub 2008 Apr 8.
In the present study, we examined whether caspases and their upstream regulators are involved in rotenone-induced cytotoxicity. Rotenone significantly inhibited the proliferation of oral cancer cell lines in a dose-dependent manner compared to normal oral mucosal fibroblasts. Flow cytometric analysis of DNA content showed that rotenone treatment induced apoptosis following G2/M arrest. Western blotting showed activation of both the caspase-8 and caspase-9 pathways, which differed from previous studies conducted in other cell types. Furthermore, p53 protein and its downstream pro-apoptotic target, Bax, were induced in SAS cells after treatment with rotenone. Rotenone-induced apoptosis was inhibited by antioxidants (glutathione, N-acetylcysteine, and tiron). In conclusion, our results demonstrate significant involvement of caspases and their upstream regulators in rotenone-induced cytotoxicity.
在本研究中，我们检测了半胱天冬酶及其上游调节因子是否参与鱼藤酮诱导的细胞毒性作用。与正常口腔黏膜成纤维细胞相比，鱼藤酮以剂量依赖的方式显著抑制口腔癌细胞系的增殖。DNA含量的流式细胞术分析表明，鱼藤酮处理诱导细胞在G2/M期阻滞之后发生凋亡。蛋白质免疫印迹法显示半胱天冬酶-8和半胱天冬酶-9途径均被激活，这与之前在其他细胞类型中进行的研究不同。此外，在用鱼藤酮处理后的SAS细胞中，p53蛋白及其下游促凋亡靶点Bax被诱导表达。抗氧化剂（谷胱甘肽、N-乙酰半胱氨酸和钛铁试剂）可抑制鱼藤酮诱导的凋亡。总之，我们的结果表明半胱天冬酶及其上游调节因子在鱼藤酮诱导的细胞毒性中起重要作用。
