Apoptosis-inducing activity of the actin-depolymerizing agent aplyronine A and its side-chain derivatives |
| |
| Authors: | Osamu Ohno Maho Morita Kazuhiro Kitamura Toshiaki Teruya Kozo Yoneda Masaki Kita Hideo Kigoshi Kiyotake Suenaga |
| |
| Institution: | 1. Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Yokohama 223-8522, Japan;2. Faculty of Education, University of the Ryukyus, 1 Senbaru, Nishihara, Okinawa 903-0213, Japan;3. Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8571, Japan |
| |
| Abstract: | Aplyronine A (1) and mycalolide B (2), which are cytotoxic actin-depolymerizing marine macrolides, were revealed to induce apoptosis in human leukemia HL60 cells and human epithelial carcinoma HeLa S3 cells. Based on these results, actin-depolymerizing compounds were expected to exhibit apoptosis-inducing activity in cancer cells. Compounds 3–6, which were synthesized based on the side-chain structure of aplyronine A, were evaluated for their actin-depolymerizing activities in vitro and cytotoxicities against HL60 cells. The growth-inhibitory activities of 3–6 were well correlated with their actin-depolymerizing activities, and derivative 6 was shown to induce the disruption of actin filaments and apoptosis in HL60 cells. These results suggested that actin-depolymerizing agents 1, 2, and 6-induced apoptosis in HL60 cells may have been due to their actin-depolymerizing activity. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
