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Galiellalactone Inhibits Stem Cell-Like ALDH-Positive Prostate Cancer Cells.

Hellsten, Rebecka LU ; Johansson, Martin LU ; Dahlman, Anna K LU ; Sterner, Olov and Bjartell, Anders LU (2011) In PLoS One 6(7).
Abstract
Galiellalactone is a potent and specific inhibitor of STAT3 signaling which has been shown to possess growth inhibitory effects on prostate cancer cells expressing active STAT3. In this study we aimed to investigate the effect of galiellalactone on prostate cancer stem cell-like cells. We explored the expression of aldehyde dehydrogenase (ALDH) as a marker for cancer stem cell-like cells in different human prostate cancer cell lines and the effects of galiellalactone on ALDH expressing (ALDH+) prostate cancer cells. ALDH+ subpopulations were detected and isolated from the human prostate cancer cell lines DU145 and long-term IL-6 stimulated LNCaP cells using ALDEFLUOR® assay and flow cytometry. In contrast to ALDH- cells, ALDH+ prostate... (More)
Galiellalactone is a potent and specific inhibitor of STAT3 signaling which has been shown to possess growth inhibitory effects on prostate cancer cells expressing active STAT3. In this study we aimed to investigate the effect of galiellalactone on prostate cancer stem cell-like cells. We explored the expression of aldehyde dehydrogenase (ALDH) as a marker for cancer stem cell-like cells in different human prostate cancer cell lines and the effects of galiellalactone on ALDH expressing (ALDH+) prostate cancer cells. ALDH+ subpopulations were detected and isolated from the human prostate cancer cell lines DU145 and long-term IL-6 stimulated LNCaP cells using ALDEFLUOR® assay and flow cytometry. In contrast to ALDH- cells, ALDH+ prostate cancer cells showed cancer stem cell-like characteristics such as increased self-renewing and colony forming capacity and tumorigenicity. In addition, ALDH+ cells showed an increased expression of putative prostate cancer stem cell markers (CD44 and integrin α2β1). Furthermore, ALDH+ cells expressed phosphorylated STAT3. Galiellalactone treatment decreased the proportion of ALDH+ prostate cancer cells and induced apoptosis of ALDH+ cells. The gene expression of ALDH1A1 was downregulated in vivo in galiellalactone treated DU145 xenografts. These findings emphasize that targeting the STAT3 pathway in prostate cancer cells, including prostate cancer stem cell-like cells, is a promising therapeutic approach and that galiellalactone is an interesting compound for the development of future prostate cancer drugs. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
PLoS One
volume
6
issue
7
publisher
Public Library of Science
external identifiers
  • WOS:000292680900030
  • PMID:21779382
  • Scopus:79960129491
ISSN
1932-6203
DOI
10.1371/journal.pone.0022118
language
English
LU publication?
yes
id
6fe49d95-13fd-4d51-9c79-ecd5520ebe58 (old id 2058339)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21779382?dopt=Abstract
date added to LUP
2011-08-01 20:26:14
date last changed
2017-02-26 04:27:17
@article{6fe49d95-13fd-4d51-9c79-ecd5520ebe58,
  abstract     = {Galiellalactone is a potent and specific inhibitor of STAT3 signaling which has been shown to possess growth inhibitory effects on prostate cancer cells expressing active STAT3. In this study we aimed to investigate the effect of galiellalactone on prostate cancer stem cell-like cells. We explored the expression of aldehyde dehydrogenase (ALDH) as a marker for cancer stem cell-like cells in different human prostate cancer cell lines and the effects of galiellalactone on ALDH expressing (ALDH+) prostate cancer cells. ALDH+ subpopulations were detected and isolated from the human prostate cancer cell lines DU145 and long-term IL-6 stimulated LNCaP cells using ALDEFLUOR® assay and flow cytometry. In contrast to ALDH- cells, ALDH+ prostate cancer cells showed cancer stem cell-like characteristics such as increased self-renewing and colony forming capacity and tumorigenicity. In addition, ALDH+ cells showed an increased expression of putative prostate cancer stem cell markers (CD44 and integrin α2β1). Furthermore, ALDH+ cells expressed phosphorylated STAT3. Galiellalactone treatment decreased the proportion of ALDH+ prostate cancer cells and induced apoptosis of ALDH+ cells. The gene expression of ALDH1A1 was downregulated in vivo in galiellalactone treated DU145 xenografts. These findings emphasize that targeting the STAT3 pathway in prostate cancer cells, including prostate cancer stem cell-like cells, is a promising therapeutic approach and that galiellalactone is an interesting compound for the development of future prostate cancer drugs.},
  articleno    = {e22118},
  author       = {Hellsten, Rebecka and Johansson, Martin and Dahlman, Anna K and Sterner, Olov and Bjartell, Anders},
  issn         = {1932-6203},
  language     = {eng},
  number       = {7},
  publisher    = {Public Library of Science},
  series       = {PLoS One},
  title        = {Galiellalactone Inhibits Stem Cell-Like ALDH-Positive Prostate Cancer Cells.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0022118},
  volume       = {6},
  year         = {2011},
}