多不饱和脂肪酸的癌症化学预防作用。

Cancer chemopreventive effects of polyunsaturated fatty acids.

作者信息

Akihisa Toshihiro, Tokuda Harukuni, Ogata Masakazu, Ukiya Motohiko, Iizuka Masao, Suzuki Takashi, Metori Koichi, Shimizu Naoto, Nishino Hoyoku

机构信息

College of Science and Technology, Nihon University, 1-8 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan.

出版信息

Cancer Lett. 2004 Mar 8;205(1):9-13. doi: 10.1016/S0304-3835(03)00284-2.

DOI:10.1016/S0304-3835(03)00284-2

PMID:15036655

Abstract

The inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), in Raji cells as a primary screening test for anti-tumor promoters, for 22 fatty acids (as free and esterified forms), including 10 di- and polyunsaturated acids, and the inhibitory effects on activation of (+/-)-(E)-methtyl-2-[(E)-hydroxy-imino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators, for 17 fatty acids (as methyl ester forms), were evaluated. Among the fatty acids tested, three n-3 polyunsaturated acids, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), exhibited potent inhibitory effects both on EBV-EA and NOR 1 activation. Furthermore, DHA methyl ester exhibited remarkable anti-tumor-promoting activity on an in vivo two-stage carcinogenesis test of mouse tumor using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.

摘要

作为抗肿瘤启动子的初步筛选试验，评估了22种脂肪酸（游离和酯化形式，包括10种二不饱和和多不饱和酸）对肿瘤启动子12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的拉吉细胞中爱泼斯坦-巴尔病毒早期抗原（EBV-EA）激活的抑制作用；作为抗肿瘤引发剂的初步筛选试验，评估了17种脂肪酸（甲酯形式）对一氧化氮（NO）供体（+/-）-（E）-甲基-2-[(E)-羟基-亚氨基]-5-硝基-6-甲氧基-3-己烯酰胺（NOR 1）激活的抑制作用。在所测试的脂肪酸中，三种n-3多不饱和酸，即二十碳五烯酸（EPA）、二十二碳五烯酸（DPA）和二十二碳六烯酸（DHA），对EBV-EA和NOR 1激活均表现出强效抑制作用。此外，DHA甲酯在以7,12-二甲基苯并[a]蒽（DMBA）为引发剂、TPA为启动子的小鼠肿瘤体内两阶段致癌试验中表现出显著的抗肿瘤促进活性。