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 commonmechanisms 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.

Apoptosis and modulation of cell cycle control by bile acids in human leukemia T cells.

FIMOGNARI, CARMELA;LENZI, MONIA;CANTELLI FORTI, GIORGIO;HRELIA, PATRIZIA
2009

Abstract

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 commonmechanisms 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.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
FIMOGNARI C.; M. LENZI; G. CANTELLI FORTI; P. HRELIA
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/78524
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