Cucurbitacin B induces G2 arrest and apoptosis via a reactive oxygen species-dependent mechanism in human colon adenocarcinoma SW480 cells
Cucurbitacin B induces G2 arrest and apoptosis via a reactive oxygen species-dependent mechanism in human colon adenocarcinoma SW480 cells
复制标题
DOI：
10.1002/mnfr.200900165
复制
发表时间：
2010-04-01
影响因子：
5.2
通讯作者：
Sakai, Toshiyuki
中科院分区：
文献类型：
--
作者：
Yasuda, Shusuke;Yogosawa, Shingo;Sakai, Toshiyuki
葫芦素B(CucB)是葫芦科蔬菜中的一种三萜类成分，是一种很有前途的抗癌植物化学物质。然而，cucB的抗肿瘤活性机制尚不清楚，尤其是在结肠癌中。在这里，我们首次证明了cucB抑制人结肠癌SW480细胞的生长是通过依赖于ROS的机制实现的。CucB以剂量依赖的方式诱导G(2)期阻滞和细胞凋亡。在分子水平上，cucB降低了SW480细胞周期蛋白B1和cdc25C蛋白的表达，并激活了caspase。另一方面，信号转导和转录激活因子3(STAT3)的磷酸化状态没有变化。我们发现，cucB增加了细胞内ROS水平，而众所周知的抗氧化剂N-乙酰半胱氨酸减少了分子表达的变化，并抑制了G(2)期停滞和细胞凋亡。这些结果表明，cucB通过STAT3非依赖但ROS依赖的机制诱导SW480细胞G(2)期停滞和凋亡。
Cucurbitacin B (cucB) is a triterpenoid constituent of Cucurbitaceae vegetables and a promising phytochemical for cancer prevention. However, the mechanism of anti-tumor activity of cucB remains unknown, especially in colon cancers. Here, we demonstrate for the first time that cucB inhibited growth of human colon cancer SW480 cells through a reactive oxygen species (ROS)-dependent mechanism. CucB induced G(2) phase arrest and apoptosis in a dose-dependent manner. At the molecular level, cucB reduced the expression of cyclin B1 and cdc25C proteins and activated caspases in SW480 cells. On the other hand, the state of phosphorylation of signaling transducer and activator of transcription 3 (STAT3) was unchanged. We found that cucB increased intracellular ROS levels, and N-acetylcysteine, a well-known antioxidant, reduced the changes in expression of the molecules, and suppressed both G(2) arrest and apoptosis. These results suggested that cucB induced G(2) arrest and apoptosis through a STAT3-independent but ROS-dependent mechanism in SW480 cells.