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Bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells

Goldberg, Alexander A.; Titorenko, Vladimir I; Beach, Adam; Sanderson, J. Thomas (2013). Bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells PeerJ , vol. 1 . e122. DOI: 10.7717/peerj.122.

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Résumé

Prostate cancer is a prevalent age-related disease in North America, accounting for about 15% of all diagnosed cancers. We have previously identified lithocholic acid (LCA) as a potential chemotherapeutic compound that selectively kills neuroblastoma cells while sparing normal human neurons. Now, we report that LCA inhibits the proliferation of androgen-dependent (AD) LNCaP prostate cancer cells and that LCA is the most potent bile acid with respect to inducing apoptosis in LNCaP as well as androgen-independent (AI) PC-3 cells, without killing RWPE-1 immortalized normal prostate epithelial cells. In LNCaP and PC-3 cells, LCA triggered the extrinsic pathway of apoptosis and cell death induced by LCA was partially dependent on the activation of caspase-8 and -3. Moreover, LCA increased cleavage of Bid and Bax, down-regulation of Bcl-2, permeabilization of the mitochondrial outer membrane and activation of caspase-9. The cytotoxic actions of LCA occurred despite the inability of this bile acid to enter the prostate cancer cells with about 98% of the nominal test concentrations present in the extracellular culture medium. With our findings, we provide evidence to support a mechanism of action underlying the broad anticancer activity of LCA in various human tissues.

Type de document:
Mots-clés libres: Apoptosis; Bile acids; Cell death; Chemotherapy; Cytotoxicity; Extracellular; In vitro; Lithocholic acid; Mitochondrial membrane permeability; Prostate cancer
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 08 mars 2016 21:15
Dernière modification: 05 juill. 2017 14:53
URI: http://espace.inrs.ca/id/eprint/2909

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