Hyun Usok, Lee Dong-Hyun, Lee Chan, Shin Cha-Gyun
Department of Biotechnology, Chung-Ang University, Kyunggi, Republic of Korea.
Toxicon. 2009 Jun;53(7-8):723-8. doi: 10.1016/j.toxicon.2009.02.012. Epub 2009 Feb 25.
Enniatins are cyclic peptides isolated from bacteria, fungi, and plants, with numerous biological effects on animal systems. Recently, we have reported that certain enniatins (ENs), such as EN H and EN MK1688, have cytotoxic effects on several adenocarcinoma cell lines. In an effort to understand the mechanism behind their cytotoxicity, we investigated whether ENs can induce apoptosis in human colorectal carcinoma cells (HCT-15 cells). Treatment with the ENs H and MK1688 resulted in an alteration of cellular and nuclear morphology, leading to an increase in the number of the cells with apoptotic nuclei (seen as condensed or fragmented nuclei). Furthermore, it was observed that cellular DNA fragmentation increased in a dose-dependent manner in EN treated cells. These cells have elevated activity levels for caspase-3, the enzyme responsible for initiating cell death, compared with the untreated cells. Normal caspase-3 activity levels were observed when Z-VAD-FMK, a caspase inhibitor, was added simultaneously with the ENs. Based on our results, we propose that the new ENs H and MK1688 induce cytotoxicity via an apoptotic pathway.
恩镰孢菌素是从细菌、真菌和植物中分离出的环肽，对动物系统具有多种生物学效应。最近，我们报道了某些恩镰孢菌素（ENs），如EN H和EN MK1688，对几种腺癌细胞系具有细胞毒性作用。为了了解其细胞毒性背后的机制，我们研究了ENs是否能诱导人结肠癌细胞（HCT-15细胞）凋亡。用EN H和MK1688处理导致细胞和细胞核形态改变，导致凋亡细胞核（表现为浓缩或碎片化的细胞核）的细胞数量增加。此外，观察到在EN处理的细胞中，细胞DNA片段化呈剂量依赖性增加。与未处理的细胞相比，这些细胞中负责启动细胞死亡的酶caspase-3的活性水平升高。当与ENs同时添加caspase抑制剂Z-VAD-FMK时，观察到caspase-3的活性水平正常。基于我们的结果，我们提出新的ENs H和MK1688通过凋亡途径诱导细胞毒性。
