Amala Cancer Research Centre, Amala Nagar, Thrissur-680555, Kerala State, India.
J Environ Pathol Toxicol Oncol. 2011;30(1):21-31. doi: 10.1615/jenvironpatholtoxicoloncol.v30.i1.30.
The objective of this study was to assess the effect of OA, a triterpene on inducing apoptosis in B16F-10 melanoma cells. Treatment of B16F-10 cells with nontoxic concentration of OA showed the presence of apoptotic bodies and induced DNA fragmentation in a dose-depended manner. Cell cycle analysis and TUNEL assay also confirmed the observation. The apoptotic genes p53, BAX, caspase-9, and caspase-3 were found upregulated in oleanolic acid–treated cells, whereas the antiapoptotic gene Bcl-2 was downregulated. OA treatment also showed a downregulation of Cyclin D1 expression and upregulated p21 and p27 gene expression in B16F-10 melanoma cells. OA inhibited the activation and nuclear translocation of transcription factors such asNF-κB, c-fos, ATF-2, and CREB-1, and also downregulated the production and expression of TNF-α, IL-1β,IL-6, and GM-CS. These results suggest that OA induces apoptosis through activating the p53-induced caspase mediated proapoptotic pathway and suppression of the NF-κB–nduced Bcl-2–ediated antiapoptotic pathway
本研究旨在评估 OA（一种三萜烯）对 B16F-10 黑素瘤细胞凋亡的影响。用无毒浓度的 OA 处理 B16F-10 细胞，可观察到凋亡小体的存在，并呈剂量依赖性诱导 DNA 片段化。细胞周期分析和 TUNEL 检测也证实了这一观察结果。在经齐墩果酸处理的细胞中，凋亡基因 p53、BAX、caspase-9 和 caspase-3 的表达上调，而抗凋亡基因 Bcl-2 的表达下调。OA 处理还可下调 B16F-10 黑素瘤细胞中细胞周期蛋白 D1 的表达，上调 p21 和 p27 基因的表达。OA 抑制转录因子如 NF-κB、c-fos、ATF-2 和 CREB-1 的激活和核易位，还下调 TNF-α、IL-1β、IL-6 和 GM-CSF 的产生和表达。这些结果表明，OA 通过激活 p53 诱导的 caspase 介导的促凋亡途径和抑制 NF-κB 诱导的 Bcl-2 介导的抗凋亡途径诱导细胞凋亡。
