Anti-cancer effects of tocotrienol in p53, iNOS knock out fibrobrasts.

生育三烯醇是维生素E和生育酚的天然化合物。以往的研究表明，生育三烯醇不仅具有心血管保护作用，还具有抗癌作用。我们研究了生育三烯醇在结肠上皮细胞和间质细胞中的抗肿瘤作用，因为结直肠癌是第三常见的癌症类型。在人结肠腺癌HT29细胞中，β生育三烯醇诱导细胞凋亡，但不诱导细胞周期停滞，并通过激活caspase-9、-3和-7来诱导细胞凋亡。半胱氨酸氨基转移酶抑制剂可阻断生育三烯醇的抗增殖作用。据报道，基质细胞产生的环氧合酶-2可促进肠上皮细胞的肿瘤进展。在p53缺失的小鼠胚胎成纤维细胞中，β-生育三烯醇通过降低亚硝酸盐浓度，降低了环氧合酶-2蛋白的表达和前列腺素E_2的浓度，提示生育三烯醇对结肠腺癌细胞有直接的抑制作用，对基质细胞有间接的环氧合酶-2抑制作用。

Tocotrienols is one class of natural compound of vitamin E, together with tocopherols. Previous studies showed that tocotrienols exert not only cardiovascular protective effects but also anti-cancer effects. We investigated the antitumor actions of tocotrienols both in colon epithelial cells and in stromal cells, since colorectal cancer is the third most common type of cancer.In human colon adenocarcinoma HT29 cells, delta-tocotrienol induced apoptosis but not cell cycle arrest, and apoptosis was induced thought activating caspase-9, -3, and -7. Caspase inhibitors canceled the antiproliferative effect of tocotrienol.Cyclooxygenase-2 produced by stromal cells has been reported to promote tumorigenic progression of intestinal epithelial cells. In mouse embryonic fibroblasts (MEFs), which were p53-deficient, delta-tocotrienol treatment reduced cyclooxygenese-2 proteins expression and prostaglandin E2 concentrations though lowering nitrite concentration.These data suggest that tocotrienol appears to have direct antiproliferative effect on colon adenocarcinoma cells and indirect cyclooxygenase-2 suppressive effect on stromal cells.