Dietary carotenoids inhibit neoplastic transformation and modulate gene expression in mouse and human cells.
Dietary carotenoids inhibit neoplastic transformation and modulate gene expression in mouse and human cells.
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DOI：
10.1093/ajcn/62.6.1327s
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发表时间：
1995-12
期刊：
影响因子：
--
通讯作者：
J. Bertram;H. Bortkiewicz
中科院分区：
文献类型：
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作者：
J. Bertram;H. Bortkiewicz
许多流行病学研究表明，食用富含水果和绿色和黄色蔬菜的饮食与降低癌症风险有关。在这种饮食的许多成分中，类胡萝卜素的含量，特别是β-胡萝卜素的含量，与降低风险的联系最为一致。目前，这种保护的生物学机制尚不清楚。存在多种可能性：类胡萝卜素是有效的抗氧化剂，已知氧化应激有助于致癌；许多类胡萝卜素可以转化为维甲酸，这些在几个解剖部位是已知的癌症防御剂；类胡萝卜素可能在哺乳动物细胞中具有额外的作用。在体外模型系统中，我们发现具有和不具有维生素A原活性的类胡萝卜素抑制致癌物诱导的肿瘤转化，抑制质膜脂质氧化，并导致缝隙连接结构单位编码基因连接蛋白43表达上调。这最后一种活性与抑制肿瘤转化的能力在统计学上相关。在人类细胞中也显示出活性：在成纤维细胞中，连接蛋白43的表达也被上调，而在器官型培养的人角质形成细胞中，β-胡萝卜素和角黄素以一种与维甲酸类似的方式调节分化。这些结果强烈表明，类胡萝卜素在人类体内具有内在的癌症化学预防作用。
Many epidemiologic studies have associated the consumption of diets rich in fruit and green and yellow vegetables with a decreased risk of cancer. Of the many components of such a diet, the content of carotenoids, particularly beta-carotene, has been most consistently linked to decreased risk. The biological mechanism for such protection is currently unclear. Multiple possibilities exist: carotenoids are potent antioxidants and oxidative stress is known to contribute to carcinogenesis; many carotenoids can be converted to retinoids, these are known cancer preventive agents at several anatomic sites; and carotenoids may possess additional actions in mammalian cells. In a model in vitro system we showed that carotenoids both with and without provitamin A activity inhibit carcinogen-induced neoplastic transformation, inhibit plasma membrane lipid oxidation, and cause up-regulated expression of connexin 43, a gene coding for the structural unit of a gap junction. This last activity was statistically correlated with the ability to inhibit neoplastic transformation. Activity has also been shown in human cells: in fibroblasts CONNEXIN 43 expression is also up-regulated whereas in human keratinocytes grown in organotypic culture beta-carotene and canthaxanthin modulate differentiation in a manner qualitatively similar to that of retinoids. These results strongly suggest that carotenoids have intrinsic cancer chemopreventive action in humans.