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首页> 外文期刊>Cancer prevention research. >Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways
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Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways

机译：葡萄籽原花青素提取物通过调节前列环素和15-HETE类花生酸途径介导抗肿瘤作用

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摘要

Grape seed procyanidin extract (GSE) has been reported to exert antineoplastic properties via the inhibition of cyclooxygenase-2 (COX-2)/prostaglandin E-2 (PGE(2)) eicosanoid pathways. In addition, ample data link carcinogenesis to inflammatory events involving other major eicosanoid metabolic pathways, including prostacyclin (PGI(2)) and 15-hydroxyeicosatetraenoic acid (15-HETE). We therefore evaluated the effects of GSE on prostacyclin synthase (PTGIS)/PGI(2) and 15-lipoxigenase-2 (15-LOX-2)/15-HETE productions by human lung premalignant and malignant cells and correlated the findings with antiproliferative or proapoptotic effects of GSE. The effects of GSE on PGI(2) and 15-HETE productions by human bronchoalveolar lavage (BAL) cells ex vivo were also determined. We further evaluated the bioactivity of oral administration of leucoselect phytosome (a standardized GSE) in the lungs of subjects participating in a lung cancer chemoprevention trial, by comparing the antiproliferative effects of coculturing matched pre-versus posttreatment BAL fluids with lung premalignant and malignant cells. GSE significantly increased PGI2 (as measured by 6-keto PGF1 alpha) and 15-HETE productions by these cells. Transfections of PTGIS or 15-LOX-2-specific siRNA partially abrogated the antiproliferative or proapoptotic effects of GSE in lung premalignant and malignant cells, respectively. GSE also increased PTGIS and inhibition of caspase-3, and transfection of 15-LOX-2 siRNA abrogated the GSE-induced apoptosis in A549 cells. In addition, culture supernatants from ex vivo GSE-treated baseline BAL cells, as well as BAL fluids from subjects treated with leucoselect phytosome, significantly decreased proliferations of lung premalignant and malignant cells. Our findings support the continued investigation of GSE as an anti-neoplastic and chemopreventive agent against lung cancer.
机译：据报道，葡萄籽原花青素提取物（GSE）通过抑制环氧合酶2（COX-2）/前列腺素E-2（PGE（2））类花生酸途径发挥抗肿瘤作用。此外，充足的数据将癌变与涉及其他主要类花生酸代谢途径（包括前列环素（PGI（2））和15-羟基二十碳四烯酸（15-HETE））的炎症事件相关联。因此，我们评估了GSE对人肺癌前和恶性细胞前列环素合酶（PTGIS）/ PGI（2）和15-lipoxigenase-2（15-LOX-2）/ 15-HETE产生的影响，并将结果与​​抗增殖或GSE的促凋亡作用。还确定了GSE对离体人支气管肺泡灌洗（BAL）细胞的PGI（2）和15-HETE产生的影响。我们通过比较匹配的治疗前后BAL液与肺癌前和恶性细胞共培养的抗增殖作用，进一步评估了在参加肺癌化学预防试验的受试者的肺中口服给予leucoselect phytosome（标准化GSE）的生物活性。 GSE显着增加了这些细胞产生的PGI2（通过6-keto PGF1α测量）和15-HETE产生。 PTGIS或15-LOX-2特异性siRNA的转染部分消除了GSE在肺癌前和恶性细胞中的抗增殖或凋亡作用。 GSE还增加了PTGIS和对caspase-3的抑制作用，而15-LOX-2 siRNA的转染消除了GSE诱导的A549细胞凋亡。另外，来自离体GSE处理的基线BAL细胞的培养上清液，以及来自经无色选择质体处理的受试者的BAL液，显着降低了肺癌前和恶性细胞的增殖。我们的发现支持对GSE作为针对肺癌的抗肿瘤和化学预防剂的持续研究。

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