Celastrol induces apoptosis in non-small-cell lung cancer A549 cells through activation of mitochondria- and Fas/FasL-mediated pathways

作者：Mou, Haibo; Zheng, Yi; Zhao, Peng; Bao, Hanying; Fang, Weijia; Xu, Nong^*

来源：Toxicology in Vitro, 2011, 25(5): 1027-1032.

DOI：10.1016/j.tiv.2011.03.023

• Celastrol
• Apoptosis
• Mitochondria
• Fas/FasL
• A549
• Lung cancer

Celastrol is a natural compound extracted from the traditional Chinese medicinal herb, Tripterygium wilfordii Hook. It has attracted interests for its potential anti-inflammatory and antitumor effects. However, the molecular mechanisms of celastrol-induced apoptosis in cancer cells remain unclear. In this study, we investigated the effects of celastrol on the human non-small-cell lung cancer (NSCLC) cell line A549 in vitro. Celastrol caused a dose- and time-dependent growth inhibition of A549 cells with an IC50 of 2.12 mu M at 48 h treatment. Celastrol induced A549 cells apoptosis as confirmed by annexin V/propidium iodide staining and DNA fragmentation. Celastrol-induced apoptosis was characterized by cleavage of caspase-9, caspase-8, caspase-3, and PARP protein, increased Fas and FasL expression, and a reduction in the mitochondrial membrane potential. Furthermore, celastrol induced the release of cytochrome c. Celastrol also up-regulated the expression of pro-apoptotic Bax, down-regulated anti-apoptotic Bcl-2, and inhibited Akt phosphorylation. These results demonstrate that celastrol can induce apoptosis of human NSCLC A549 cells through activation of both mitochondria- and FasL-mediated pathways.

• 出版日期2011-8
• 单位浙江大学