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Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide

Acid ceramidase (AC) over-expression has been observed in prostate cancer cell lines and primary tumors, and contributes to resistance to chemotherapy and radiation. The consequence of AC over-expression is the ability to convert ceramide, which is often produced as a pro-apoptotic response to stres...

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Autores principales: Turner, Lorianne S., Cheng, Joseph C., Beckham, Thomas H., Norris, James S., Liu, Xiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203650/
https://www.ncbi.nlm.nih.gov/pubmed/21116286
http://dx.doi.org/10.1038/pcan.2010.47
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author Turner, Lorianne S.
Cheng, Joseph C.
Beckham, Thomas H.
Norris, James S.
Liu, Xiang
author_facet Turner, Lorianne S.
Cheng, Joseph C.
Beckham, Thomas H.
Norris, James S.
Liu, Xiang
author_sort Turner, Lorianne S.
collection PubMed
description Acid ceramidase (AC) over-expression has been observed in prostate cancer cell lines and primary tumors, and contributes to resistance to chemotherapy and radiation. The consequence of AC over-expression is the ability to convert ceramide, which is often produced as a pro-apoptotic response to stress, to sphingosine, which can then be converted to the pro-survival molecule sphingosine-1-phosphate. In addition to their ability to metabolize ceramide produced in response to stress, we show here that prostate cancer cell lines over-expressing acid ceramidase also have increased lysosomal density and increased levels of autophagy. Furthermore, pre-treatment with 3-methyladenine restores sensitivity of these cells to treatment with C(6)-ceramide. We also observed increased expression of the lysosomal stabilizing protein KIF5B and increased sensitivity to the lysosomotropic agent LCL385. Thus, we conclude that acid ceramidase over-expression increases autophagy in prostate cancer cells, and that increased autophagy enhances resistance to ceramide.
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spelling pubmed-42036502014-10-20 Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide Turner, Lorianne S. Cheng, Joseph C. Beckham, Thomas H. Norris, James S. Liu, Xiang Prostate Cancer Prostatic Dis Article Acid ceramidase (AC) over-expression has been observed in prostate cancer cell lines and primary tumors, and contributes to resistance to chemotherapy and radiation. The consequence of AC over-expression is the ability to convert ceramide, which is often produced as a pro-apoptotic response to stress, to sphingosine, which can then be converted to the pro-survival molecule sphingosine-1-phosphate. In addition to their ability to metabolize ceramide produced in response to stress, we show here that prostate cancer cell lines over-expressing acid ceramidase also have increased lysosomal density and increased levels of autophagy. Furthermore, pre-treatment with 3-methyladenine restores sensitivity of these cells to treatment with C(6)-ceramide. We also observed increased expression of the lysosomal stabilizing protein KIF5B and increased sensitivity to the lysosomotropic agent LCL385. Thus, we conclude that acid ceramidase over-expression increases autophagy in prostate cancer cells, and that increased autophagy enhances resistance to ceramide. 2010-11-30 2011-03 /pmc/articles/PMC4203650/ /pubmed/21116286 http://dx.doi.org/10.1038/pcan.2010.47 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Turner, Lorianne S.
Cheng, Joseph C.
Beckham, Thomas H.
Norris, James S.
Liu, Xiang
Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide
title Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide
title_full Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide
title_fullStr Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide
title_full_unstemmed Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide
title_short Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide
title_sort autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to c(6)-ceramide
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203650/
https://www.ncbi.nlm.nih.gov/pubmed/21116286
http://dx.doi.org/10.1038/pcan.2010.47
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