Fimognari Carmela, Lenzi Monia, Cantelli-Forti Giorgio, Hrelia Patrizia
Department of Pharmacology, University of Bologna, Bologna, Italy.
Ann N Y Acad Sci. 2009 Aug;1171:264-9. doi: 10.1111/j.1749-6632.2009.04710.x.
Depending on the nature of chemical structures, different bile acids exhibit distinct biological effects. Their therapeutic efficacy has been widely demonstrated in various liver diseases, suggesting that they might protect hepatocytes against common mechanisms of liver damage. Although it has been shown to prevent apoptotic cell death in certain cell lines, bile acids significantly inhibited cell growth and induced apoptosis in cancer cells. To better understand the pharmacological potential of bile acids in cancer cells, we investigated and compared the effects of deoxycholic acid (DCA), ursodeoxycholic acid (UDCA), and their taurine-derivatives [taurodeoxycholic acid (TDCA) and tauroursodeoxycholic acid (TUDCA), respectively] on the induction of apoptosis and inhibition of cell proliferation of a human T leukemia cell line (Jurkat cells). All the bile acids tested induced a delay in cell cycle progression. Moreover, DCA markedly increased the fraction of apoptotic cells. The effects of TDCA, UDCA, and TUDCA were different from those observed for DCA. Their primary effect was the induction of necrosis. These distinctive features suggest that the hydrophobic properties of DCA play a role in its cytotoxic potential and indicate that it is possible to create new drugs useful for cancer therapy from bile acid derivatives as lead compounds.
根据化学结构的性质，不同的胆汁酸表现出不同的生物学效应。它们的治疗效果已在各种肝脏疾病中得到广泛证明，这表明它们可能保护肝细胞免受常见的肝损伤机制影响。尽管已证明胆汁酸可防止某些细胞系中的凋亡细胞死亡，但它们在癌细胞中显著抑制细胞生长并诱导凋亡。为了更好地了解胆汁酸在癌细胞中的药理潜力，我们研究并比较了脱氧胆酸（DCA）、熊去氧胆酸（UDCA）及其牛磺酸衍生物[分别为牛磺脱氧胆酸（TDCA）和牛磺熊去氧胆酸（TUDCA）]对人T白血病细胞系（Jurkat细胞）凋亡诱导和细胞增殖抑制的影响。所有测试的胆汁酸均导致细胞周期进程延迟。此外，DCA显著增加了凋亡细胞的比例。TDCA、UDCA和TUDCA的作用与DCA不同。它们的主要作用是诱导坏死。这些独特的特征表明DCA的疏水性在其细胞毒性潜力中起作用，并表明有可能从胆汁酸衍生物作为先导化合物开发出对癌症治疗有用的新药。
