Inhibitory effect of caffeic acid esters on azoxymethane-induced biochemical changes and aberrant crypt foci formation in rat colon.
Inhibitory effect of caffeic acid esters on azoxymethane-induced biochemical changes and aberrant crypt foci formation in rat colon.
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发表时间：
1993-09
期刊：
影响因子：
11.2
通讯作者：
C. Rao;D. Desai;B. Simi;Nalini Kulkarni;S. Amin;B. Reddy
中科院分区：
文献类型：
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作者：
C. Rao;D. Desai;B. Simi;Nalini Kulkarni;S. Amin;B. Reddy
本实验室以前的工作确定，咖啡酸酯，目前在蜜蜂蜂箱的油脂，是人类结肠肿瘤细胞生长的有效抑制剂，这表明这些化合物可能具有抗结肠癌的抗肿瘤活性。本研究旨在观察咖啡酸甲酯（MC）和咖啡酸苯乙酯（PEC）对氧化偶氮甲烷（AOM）诱导的雄性F344大鼠肝脏和结肠粘膜鸟氨酸脱羧酶（ODC）、酪氨酸蛋白激酶（TPK）和花生四烯酸代谢的抑制作用;和二甲基咖啡酸苯乙酯（PEDMC）对肝脏和结肠粘膜中花生四烯酸体外代谢的影响，以及（c）PEC、PEMC和PEDMC对AOM诱导的F344大鼠结肠异常隐窝灶（ACF）形成的影响。在5周龄时，对动物组饲喂含有600 ppm MC或PEC（生化研究）或500 ppm PEC、PEMC或PEDMC（ACF研究）的饲料。两周后，除溶媒给药组外，所有动物均接受s.c.注射AOM，每周一次，持续2周。5天后处死拟用于生化研究的动物，并分析结肠粘膜和肝脏的ODC、TPK、脂氧合酶和环氧合酶代谢产物。9周后处死预期用于ACF研究的动物，并分析结肠中的ACF。结果表明，PEC饲料显著抑制AOM诱导的肝脏和结肠ODC（P < 0.05）和TPK（P < 0.001）活性。PEC饲料显著（P < 0.001）抑制AOM诱导的脂氧合酶代谢产物8（S）-和12（S）-羟基二十碳四烯酸（HETE）。饲喂MC饲料的动物对ODC和5（S）-、8（S）-、12（S）-和15（S）-HETE表现出中度抑制作用，对结肠TPK活性表现出显著（P < 0.001）作用。然而，MC和PEC饮食对环氧合酶代谢没有显着的抑制作用。在体外研究中，咖啡酸和MC仅在100 μ M浓度下显示出对HETE形成的抑制作用，而PEC、PEMC和PEDMC以剂量依赖性方式抑制体外HETE形成。AOM诱导的结肠ACF在喂食PEC（55%）、PEMC（82%）或PEDMC（81%）的动物中被显著抑制。本研究的结果表明，PEC，PEMC和PEDMC，蜂蜜中存在，抑制AOM诱导的结肠癌前病变，ODC，TPK和脂氧合酶的活性，这是相关的结肠癌发生。
Previous work from this laboratory established that caffeic acid esters, present in the propolis of honey bee hives, are potent inhibitors of human colon tumor cell growth, suggesting that these compounds may possess antitumor activity against colon carcinogenesis. The present study was designed to investigate (a) the inhibitory effects of methyl caffeate (MC) and phenylethyl caffeate (PEC) on azoxymethane (AOM)-induced ornithine decarboxylase (ODC), tyrosine protein kinase (TPK), and arachidonic acid metabolism in liver and colonic mucosa of male F344 rats, (b) the effects of caffeic acid, MC, PEC, phenylethyl-3-methylcaffeate (PEMC), and phenylethyl dimethylcaffeate (PEDMC) on in vitro arachidonic acid metabolism in liver and colonic mucosa, and (c) the effects of PEC, PEMC, and PEDMC on AOM-induced aberrant crypt foci (ACF) formation in the colon of F344 rats. At 5 weeks of age, groups of animals were fed diets containing 600 ppm MC or PEC (biochemical study) or 500 ppm PEC, PEMC, or PEDMC (ACF study). Two weeks later, all animals except the vehicle-treated groups were given s.c. injections of AOM, once weekly for 2 weeks. The animals intended for the biochemical study were sacrificed 5 days later and colonic mucosa and liver were analyzed for ODC, TPK, lipoxygenase, and cyclooxygenase metabolites. The animals intended for the ACF study were sacrificed 9 weeks later and analyzed for ACF in the colon. The results indicate that the PEC diet significantly inhibited AOM-induced ODC (P < 0.05) and TPK (P < 0.001) activities in liver and colon. The PEC diet significantly (P < 0.001) suppressed the AOM-induced lipoxygenase metabolites 8(S)- and 12(S)-hydroxyeicosatetraenoic acid (HETE). The animals fed the MC diet exhibited a moderate inhibitory effect on ODC and 5(S)-, 8(S)-, 12(S)-, and 15(S)-HETEs and a significant (P < 0.001) effect on colonic TPK activity. However, the MC and PEC diets showed no significant inhibitory effects on cyclooxygenase metabolism. In an in vitro study, caffeic acid and MC showed inhibitory effects on HETE formation only at a 100 microM concentration, whereas PEC, PEMC, and PEDMC suppressed in vitro HETE formation in a dose-dependent manner. AOM-induced colonic ACF were significantly inhibited in the animals fed PEC (55%), PEMC (82%), or PEDMC (81%). The results of the present study indicate that PEC, PEMC, and PEDMC, present in honey, inhibit AOM-induced colonic preneoplastic lesions, ODC, TPK, and lipoxygenase activity, which are relevant to colon carcinogenesis.