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.
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: |
Article
|
| 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: |
02 déc. 2020 14:44 |
| URI: |
http://espace.inrs.ca/id/eprint/2909 |
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