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

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Author(s): Alexander A. Goldberg | Vladimir I. Titorenko | Adam Beach | J. Thomas Sanderson

Journal: PeerJ
ISSN 2167-8359

Volume: 1;
Start page: e122;
Date: 2013;
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Keywords: Bile acids | Lithocholic acid | Apoptosis | Prostate cancer | Chemotherapy | In vitro | Cell death | Cytotoxicity | Mitochondrial membrane permeability | Extracellular

ABSTRACT
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.

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