Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
Oncol Rep. 2011 Oct;26(4):919-24. doi: 10.3892/or.2011.1358. Epub 2011 Jun 23.
Asterosaponin 1, a new cytostatic agent from starfish, possesses several bioactivities including an antitumor effect. The aim of this study was to investigate the potential anti-proliferative and pro-apoptotic activity of asterosaponin 1 in A549 human lung cancer cells, as well as the potential mechanisms. The results showed that asterosaponin 1 inhibited the proliferation of A549 cells in a dose-dependent manner, and the cytostatic activity resulted from the induction of apoptotic cell death. Asterosaponin 1 increased ER dilation and cytosolic Ca2+ concentration, and enhanced the expression of the ER molecular chaperones GRP78 and GRP94 in a dose- and time-dependent manner. In addition, asterosaponin 1 treated A549 cells exerted increased expression and activity of CHOP, caspase-4 and JNK, three essential ER-associated apoptotic molecules. In summary, these results demonstrated that asterosaponin 1 inhibits the proliferation of A549 cells through induction of ER stress-associated apoptosis, making asterosaponin 1 a candidate new anticancer drug for lung cancer therapy.
海星甾苷 1 是一种新型的具有多种生物活性的细胞抑制剂，包括抗肿瘤作用。本研究旨在探讨海星甾苷 1 在人肺癌 A549 细胞中的潜在抗增殖和促凋亡活性及其可能的机制。结果表明，海星甾苷 1 呈剂量依赖性抑制 A549 细胞的增殖，细胞抑制活性是通过诱导细胞凋亡导致的。海星甾苷 1 以剂量和时间依赖的方式增加内质网扩张和胞质 Ca2+浓度，并增强内质网分子伴侣 GRP78 和 GRP94 的表达。此外，海星甾苷 1 处理的 A549 细胞中 CHOP、caspase-4 和 JNK 的表达和活性增加，这三种蛋白是内质网相关凋亡的必需分子。综上所述，这些结果表明，海星甾苷 1 通过诱导内质网应激相关的凋亡抑制 A549 细胞的增殖，使海星甾苷 1 成为治疗肺癌的候选新型抗癌药物。
