Apoptosis-inducing activity of the actin-depolymerizing agent aplyronine A and its side-chain derivatives.
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 S(3) 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.
Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Yokohama 223-8522, Japan.
Osamu
O
Ohno
Maho
M
Morita
Kazuhiro
K
Kitamura
Toshiaki
T
Teruya
Kozo
K
Yoneda
Masaki
M
Kita
Hideo
H
Kigoshi
Kiyotake
K
Suenaga
D000199:Actins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000494:pharmacology*; D008387:Marine Toxins; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology
D000199:Actins; D000970:Antineoplastic Agents; D018942:Macrolides; D008387:Marine Toxins; D010080:Oxazoles; C080978:mycalolide B; C104057:aplyronine A