Department of Chemical Biology and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma'anshan, Anhui 243002, P.R. China.
Oncol Rep. 2017 Nov;38(5):2951-2958. doi: 10.3892/or.2017.5971. Epub 2017 Sep 19.
Celastrol, a natural compound extracted from Tripterygium wilfordii, is known to exhibit potential anticancer activities in various types of tumor cells. E2F1 is reported to be overexpressed in several types of human tumors and its inactivation may be a valuable novel potential therapeutic strategy for cancer treatment. However, the molecular mechanism underlying the pro-apoptotic effects of celastrol on hepatocellular carcinoma (HCC) cells remains unclear, and E2F1-targeted compounds have been rarely identified. In the present study, we demonstrated that celastrol inhibited the proliferation of human HCC cells and triggered apoptosis of HepG2 cells in a caspase-dependent manner. E2F1 was potently downregulated by celastrol in a dose- and time-dependent manner at both the mRNA and protein levels. Moreover, siRNA-mediated E2F1 silencing enhanced celastrol-induced apoptosis and inhibition of proliferation. Our data imply that downregulation of E2F1 may be a key factor in the celastrol-mediated inhibitory effects in HepG2 cells, and celastrol can serve as a leading compound for the development of compounds designed to inactivate E2F1 for HCC therapy.
雷公藤红素是从雷公藤中提取的一种天然化合物，已知它在多种肿瘤细胞中具有潜在的抗癌活性。E2F1 在几种人类肿瘤中过表达，其失活可能是癌症治疗的一种有价值的新潜在治疗策略。然而，雷公藤红素对肝癌 (HCC) 细胞促凋亡作用的分子机制尚不清楚，并且很少有针对 E2F1 的化合物被鉴定。在本研究中，我们证明雷公藤红素抑制人 HCC 细胞的增殖，并以 caspase 依赖性方式引发 HepG2 细胞凋亡。雷公藤红素在 mRNA 和蛋白质水平上以剂量和时间依赖的方式强烈地下调 E2F1。此外，siRNA 介导的 E2F1 沉默增强了雷公藤红素诱导的凋亡和增殖抑制。我们的数据表明，E2F1 的下调可能是雷公藤红素介导的 HepG2 细胞抑制作用的关键因素，并且雷公藤红素可以作为开发用于 HCC 治疗的旨在使 E2F1 失活的化合物的先导化合物。
