Nakai Junko, Kawada Kentaro, Nagata Seigo, Kuramochi Kouji, Uchiro Hiromi, Kobayashi Susumu, Ikekita Masahiko
Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo, Noda, Chiba, Japan.
Biochim Biophys Acta. 2002 Mar 15;1581(1-2):1-10. doi: 10.1016/s1388-1981(01)00169-x.
A novel lipid compound, epolactaene, was isolated from the culture supernatant of Penicillium sp. 1689-P and it has already been reported that it induced neurite outgrowth in a human neuroblastoma cell line. In this study, we first investigated the effects of epolactaene on a human leukemia B-cell line, BALL-1 cells, and clarified that epolactaene induces apoptosis in BALL-1 cells in a dose- and time-dependent manner. Furthermore, we focused on the side chain structure of epolactaene, and chemically synthesized epolactaene derivatives. One derivative, which has a straight long alkyl chain as its side chain, induced apoptosis more effectively than epolactaene. On the other hand, other derivatives with a short alkyl side chain had weaker apoptosis-inducing actions. A good correlation was found between the apoptosis-inducing action of these compounds and their octanol/water partition coefficients (log P). These results suggested that the apoptosis-inducing activities of epolactaene and its derivatives were related to the hydrophobicity of these compounds; so that side chain structure of epolactaene is very important for its apoptosis-inducing activities. These apoptosis-inducing actions of epolactaene and its derivatives were also observed in various blood tumor cell lines and normal lymphocytes.
一种新型脂质化合物埃坡拉酮，是从青霉菌株1689 - P的培养上清液中分离得到的，据报道它能诱导人神经母细胞瘤细胞系的神经突生长。在本研究中，我们首先研究了埃坡拉酮对人白血病B细胞系BALL - 1细胞的影响，并明确了埃坡拉酮以剂量和时间依赖性方式诱导BALL - 1细胞凋亡。此外，我们关注了埃坡拉酮的侧链结构，并化学合成了埃坡拉酮衍生物。一种以直链长烷基链作为侧链的衍生物比埃坡拉酮更有效地诱导细胞凋亡。另一方面，其他具有短烷基侧链的衍生物诱导凋亡的作用较弱。这些化合物的诱导凋亡作用与其正辛醇/水分配系数（log P）之间存在良好的相关性。这些结果表明，埃坡拉酮及其衍生物的诱导凋亡活性与这些化合物的疏水性有关；因此，埃坡拉酮的侧链结构对其诱导凋亡活性非常重要。埃坡拉酮及其衍生物的这些诱导凋亡作用在各种血液肿瘤细胞系和正常淋巴细胞中也有观察到。
