Apoptosis and modulation of cell cycle control by bile acids in human leukemia T cells.
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.
Fimognari
Carmela
C
Department of Pharmacology, University of Bologna, Bologna, Italy. carmela.fimognari@unibo.it
Lenzi
Monia
M
Cantelli-Forti
Giorgio
G
Hrelia
Patrizia
P
D017209:Apoptosis / Q000187:drug effects*; D001647:Bile Acids and Salts / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003840:Deoxycholic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000473:pathology / Q000503:physiopathology; D016196:S Phase / Q000187:drug effects; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D013657:Taurodeoxycholic Acid / Q000494:pharmacology; D014580:Ursodeoxycholic Acid / Q000494:pharmacology
D001647:Bile Acids and Salts; D003840:Deoxycholic Acid; D013655:Taurochenodeoxycholic Acid; D013657:Taurodeoxycholic Acid; C031655:ursodoxicoltaurine; D014580:Ursodeoxycholic Acid