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标题：Stereoisomer-Specific Induction of G2/M Phase Arrest and Apoptosis by 9-(E,Z)-Hydroxyoctadecadienoic Acid in Mouse Lymphoma Cells
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作者：Atsushi Kodaka ; Yuki Hayakawa ; Rawaa Jaffar AlSayegh 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2019
卷号：42
期号：6
页码：937-943
DOI：10.1248/bpb.b18-00935
出版社：The Pharmaceutical Society of Japan
摘要：Hydroxyoctadecadienoic acids (HODEs) are generated by oxidation of linoleic acid in vivo and thought to mediate various pathophysiological responses. In this study, we examined the effects of HODEs on EL4 mouse lymphoma cell growth and found that 9-( E , Z )-HODE inhibited EL4 cell growth in a dose-dependent manner, whereas no such growth inhibition was observed with other isomers (9-( E , E )-, 13-( Z , E )-, or 13-( E , E )-HODE), suggesting that the growth-inhibitory effect of HODEs was stereospecific. Analysis by flow cytometry (FACS) with annexin V and propidium iodide (PI) staining showed that 9-( E , Z )-HODE induced apoptosis with G2/M phase arrest. We next examined the growth inhibition profile of 9-( E , Z )-HODE against a panel of 39 human cancer cell lines (JFCR39). The fingerprint of growth inhibition by 9-( E , Z )-HODE exhibited a high degree of similarity to that by MLN4924, an inhibitor of NEDD8-activating enzyme. The intracellular NEDD8 (ubiquitin-like protein) expression in EL4 cells was decreased by the treatment with 9-( E , Z )-HODE as assessed by immunoblotting and flow cytometry. In conclusion, 9-( E , Z )-HODE specifically induced G2/M phase arrest and apoptosis, and the decrease of NEDD8 expression might be involved in this effect.
关键词：hydroxyoctadecadienoic acid;stereoisomer;apoptosis;G2/M arrest;lymphoma