A novel lipid compound, epolactaene, induces apoptosis: its action is modulated by its side chain structure.
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.
Nakai
Junko
J
Department of Applied Biological Science, Faculty of Science and Technology, Science University of Tokyo, Noda, Chiba, Japan.
Kawada
Kentaro
K
Nagata
Seigo
S
Kuramochi
Kouji
K
Uchiro
Hiromi
H
Kobayashi
Susumu
S
Ikekita
Masahiko
M
D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019169:Jurkat Cells; D007700:Kinetics; D015448:Leukemia, B-Cell / Q000473:pathology; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects; D011090:Polyenes / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D004852:Epoxy Compounds; D008055:Lipids; D011090:Polyenes; C095351:epolactaene