Antiproliferative activity of guava leaf extract via inhibition of prostaglandin endoperoxide H synthase isoforms
Antiproliferative activity of guava leaf extract via inhibition of prostaglandin endoperoxide H synthase isoforms
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DOI：
10.1016/j.plefa.2009.04.006
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发表时间：
2009-05-01
影响因子：
3
通讯作者：
Takahashi, Yoshitaka
中科院分区：
文献类型：
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作者：
Kawakami, Yuki;Nakamura, Tomomi;Takahashi, Yoshitaka
前列腺素内过氧化物H合成酶（PGHS）是合成前列腺素（PGs）的关键酶，在炎症和癌变中起重要作用。由于番石榴的提取物对我们的身体有多种有益的作用，包括抗炎、抗氧化和抗增殖活性，我们研究了提取物是否抑制两种PGHS异构体的催化活性，使用亚油酸作为替代底物。番石榴叶提取物抑制重组人pghs - 1和PGHS-2的环加氧酶反应，并通过亚油酸转化为9-和13-羟基十八烯二烯酸（HODEs）来评估。番石榴叶提取物还能抑制PGHS-1的PG氢过氧化物酶活性，而非甾体抗炎药（NSAIDs）对这种活性没有影响。槲皮素是其主要成分之一，不仅能抑制两种异构体的环加氧酶活性，还能部分抑制PG氢过氧化物酶活性。人结肠癌细胞中PGHS-1和PGHS-2的过表达与不表达任何同种异构体的模拟转染细胞相比，增加了DNA合成率。番石榴叶提取物不仅抑制PGE(2)的合成，而且将PGHS-1和pghs -2表达细胞的DNA合成率抑制到与模拟转染细胞相同的水平。这些结果表明番石榴叶提取物的抗增殖活性至少部分是由抑制PGHS亚型的催化活性引起的。2009爱思唯尔有限公司版权所有。
Prostaglandin endoperoxide H synthase (PGHS) is a key enzyme for the synthesis of prostaglandins (PGs) which play important roles in inflammation and carcinogenesis. Because the extract from Psidium guajava is known to have a variety of beneficial effects on our body including the anti-inflammatory, antioxidative and antiproliferative activities, we investigated whether the extract inhibited the catalytic activity of the two PGHS isoforms using linoleic acid as an alternative substrate. The guava leaf extract inhibited the cyclooxygenase reaction of recombinant human PGHS-l and PGHS-2 as assessed by conversion of linoleic acid to 9- and 13-hydroxyoctadecadienoic acids (HODEs). The guava leaf extract also inhibited the PG hydroperoxidase activity of PGHS-1, which was not affected by nonsteroidal anti-inflammatory drugs (NSAIDs). Quercetin which was one of the major components not only inhibited the cyclooxygenase activity of both isoforms but also partially inhibited the PG hydroperoxidase activity. Overexpression of human PGHS-1 and PGHS-2 in the human colon carcinoma cells increased the DNA synthesis rate as compared with mock-transfected cells which did not express any isoforms. The guava leaf extract not only inhibited the PGE(2) synthesis but also suppressed the DNA synthesis rate in the PGHS-1- and PGHS-2-expressing cells to the same level as mock-transfected cells. These results demonstrate the antiproliferative activity of the guava leaf extract which is at least in part caused by inhibition of the catalytic activity of PGHS isoforms. (C) 2009 Elsevier Ltd. All rights reserved.