Galiellalactone Inhibits Stem Cell-Like ALDH-Positive Prostate Cancer Cells.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2058339
- author
- Hellsten, Rebecka LU ; Johansson, Martin LU ; Dahlman, Anna K LU ; Sterner, Olov and Bjartell, Anders LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 6
- issue
- 7
- article number
- e22118
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000292680900030
- pmid:21779382
- scopus:79960129491
- pmid:21779382
- 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
- 2016-04-04 09:24:49
- date last changed
- 2022-03-15 19:08:53
@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.}}, 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 (PLoS)}}, series = {{PLoS ONE}}, title = {{Galiellalactone Inhibits Stem Cell-Like ALDH-Positive Prostate Cancer Cells.}}, url = {{https://lup.lub.lu.se/search/files/5317549/2220068.pdf}}, doi = {{10.1371/journal.pone.0022118}}, volume = {{6}}, year = {{2011}}, }