Cytotoxic effects of cantharidin on the growth of normal and carcinoma cells
Cytotoxic effects of cantharidin on the growth of normal and carcinoma cells
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DOI：
10.1016/s0300-483x(00)00185-2
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发表时间：
2000-06-08
期刊：
影响因子：
4.5
通讯作者：
Yang, LL
中科院分区：
文献类型：
--
作者：
Wang, CC;Wu, CH;Yang, LL
斑泻素是从斑潜蝇中分离得到的，是一种有效的肝癌细胞(Hep 3B细胞)抑制物。在本研究中，斑泻素对Hep-3B细胞和正常常肝细胞的IC50值分别为2.2mU/L和30.2mU/L。斑泻素处理Hep 3B细胞1h内即可引起细胞死亡(IC50=52.8mU/L)，提示斑泻素是一种急性细胞毒剂。我们发现斑泻素虽然能诱导细胞死亡，但不能通过细胞内掺入H-3-胸腺嘧啶核苷、H-3-尿苷或H-3-亮氨酸直接抑制核酸生物合成的活性。斑泻素处理Hep 3B细胞1h内未见明显的细胞周期改变，但36h后的细胞检测显示斑泻素可将细胞周期调节在G(2)/M期。此外，经处理的Hep 3B细胞具有圆形和缩小的外观。经处理的Hep 3B细胞微绒毛数量减少，取而代之的是大量的水泡。斑泻素治疗后的其他超微结构变化包括脂滴的存在，线粒体的肿胀和糖原颗粒的积累。本研究发现斑泻素对Hep 3B细胞线粒体有损伤作用，提示斑泻素可通过抑制线粒体能量系统对Hep 3B细胞产生急性和致死性毒性作用。综上所述，本研究证实斑泻素可抑制Hep 3B细胞周期各时相的进展。(C)2000爱思唯尔爱尔兰科学有限公司。保留所有权利。
Cantharidin is isolated from Mylabris phalerata Pallas and is a potent inhibitor of hepatocellular carcinoma cells (Hep 3B cells). In the present study, the IC50 values of cantharidin on Hep 3B cells and normal Chang liver cells were found to be 2.2 and 30.2 mu M for 36 h, respectively. Furthermore, cantharidin-treated Hep 3B cells induced cell death within 1 h (IC50 = 52.8 mu M): suggesting that cantharidin is an acute cytotoxic agent. We found that although cantharidin could induce cell death, it could not directly inhibit the activity of nucleic acid biosynthesis by the cellular incorporation of H-3-thymidine, H-3-uridine or H-3-leucine. Cantharidin-treated Hep 3B cells showed no evidence of major alterations in the cell cycle distribution within 1 h. However, examination of cells after treatment for 36 h showed that cantharidin regulated the cell cycle at the G(2)/M phase. Moreover, the treated Hep 3B cells had a rounded and shrunken appearance. The microvilli of treated Hep 3B cells were reduced in number and replaced by numerous blebs. Other ultrastructural changes following cantharidin treatment included the presence of lipid droplets, swelling of the mitochondria and accumulation of glycogen particles. The findings of damaged mitochondria in the cantharidin treated Hep 3B cells in this study suggest that cantharidin can induce acute and lethal toxic effects on Hep 3B cells by inhibiting the mitochondria energy system. In conclusion, this study had demonstrated that cantharidin could inhibit progression of all phases of the Hep 3B cell cycle. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.