title: Galiellalactone inhibits stem cell-like ALDH-positive prostate cancer cells.
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.
authors.affiliation: Division of Urological Cancers, Department of Clinical Sciences, Lund University, Malmö, Sweden. rebecka.hellsten@med.lu.se
authors.forename: Rebecka
authors.initials: R
authors.lastname: Hellsten
authors.forename: Martin
authors.initials: M
authors.lastname: Johansson
authors.forename: Anna
authors.initials: A
authors.lastname: Dahlman
authors.forename: Olov
authors.initials: O
authors.lastname: Sterner
authors.forename: Anders
authors.initials: A
authors.lastname: Bjartell
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; D050796:STAT3 Transcription Factor; C416043:galiellalactone; D000444:Aldehyde Dehydrogenase