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Bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells
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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740138/ https://www.ncbi.nlm.nih.gov/pubmed/23940835 http://dx.doi.org/10.7717/peerj.122 |
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author | Goldberg, Alexander A. Titorenko, Vladimir I. Beach, Adam Sanderson, J. Thomas |
author_facet | Goldberg, Alexander A. Titorenko, Vladimir I. Beach, Adam Sanderson, J. Thomas |
author_sort | Goldberg, Alexander A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3740138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-37401382013-08-12 Bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells Goldberg, Alexander A. Titorenko, Vladimir I. Beach, Adam Sanderson, J. Thomas PeerJ Toxicology 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. PeerJ Inc. 2013-08-08 /pmc/articles/PMC3740138/ /pubmed/23940835 http://dx.doi.org/10.7717/peerj.122 Text en © 2013 Goldberg et al. http://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Toxicology Goldberg, Alexander A. Titorenko, Vladimir I. Beach, Adam Sanderson, J. Thomas Bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells |
title | Bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells |
title_full | Bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells |
title_fullStr | Bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells |
title_full_unstemmed | Bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells |
title_short | Bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells |
title_sort | bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells |
topic | Toxicology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740138/ https://www.ncbi.nlm.nih.gov/pubmed/23940835 http://dx.doi.org/10.7717/peerj.122 |
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