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STAT3 inhibition with galiellalactone effectively targets the prostate cancer stem-like cell population

Canesin, Giacomo LU ; Maggio, Valentina ; Palominos, Macarena LU ; Stiehm, Anna LU ; Contreras, Hector R. ; Castellón, Enrique A. ; Morote, Juan ; Paciucci, Rosanna ; Maitland, Norman J. and Bjartell, Anders LU , et al. (2020) In Scientific Reports 10(1).
Abstract

Cancer stem cells (CSCs) are a small subpopulation of quiescent cells with the potential to differentiate into tumor cells. CSCs are involved in tumor initiation and progression and contribute to treatment failure through their intrinsic resistance to chemo- or radiotherapy, thus representing a substantial concern for cancer treatment. Prostate CSCs’ activity has been shown to be regulated by the transcription factor Signal Transducer and Activator of Transcription 3 (STAT3). Here we investigated the effect of galiellalactone (GL), a direct STAT3 inhibitor, on CSCs derived from prostate cancer patients, on docetaxel-resistant spheres with stem cell characteristics, on CSCs obtained from the DU145 cell line in vitro and on DU145 tumors... (More)

Cancer stem cells (CSCs) are a small subpopulation of quiescent cells with the potential to differentiate into tumor cells. CSCs are involved in tumor initiation and progression and contribute to treatment failure through their intrinsic resistance to chemo- or radiotherapy, thus representing a substantial concern for cancer treatment. Prostate CSCs’ activity has been shown to be regulated by the transcription factor Signal Transducer and Activator of Transcription 3 (STAT3). Here we investigated the effect of galiellalactone (GL), a direct STAT3 inhibitor, on CSCs derived from prostate cancer patients, on docetaxel-resistant spheres with stem cell characteristics, on CSCs obtained from the DU145 cell line in vitro and on DU145 tumors in vivo. We found that GL significantly reduced the viability of docetaxel-resistant and patient-derived spheres. Moreover, CSCs isolated from DU145 cells were sensitive to low concentrations of GL, and the treatment with GL suppressed their viability and their ability to form colonies and spheres. STAT3 inhibition down regulated transcriptional targets of STAT3 in these cells, indicating STAT3 activity in CSCs. Our results indicate that GL can target the prostate stem cell niche in patient-derived cells, in docetaxel-resistant spheres and in an in vitro model. We conclude that GL represents a promising therapeutic approach for prostate cancer patients, as it reduces the viability of prostate cancer-therapy-resistant cells in both CSCs and non-CSC populations.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
10
issue
1
article number
13958
publisher
Nature Publishing Group
external identifiers
  • scopus:85089500708
  • pmid:32811873
ISSN
2045-2322
DOI
10.1038/s41598-020-70948-5
language
English
LU publication?
yes
id
2ae6d3b1-feaf-4014-ba18-58ab85889fde
date added to LUP
2020-08-27 09:46:55
date last changed
2024-05-15 17:00:23
@article{2ae6d3b1-feaf-4014-ba18-58ab85889fde,
  abstract     = {{<p>Cancer stem cells (CSCs) are a small subpopulation of quiescent cells with the potential to differentiate into tumor cells. CSCs are involved in tumor initiation and progression and contribute to treatment failure through their intrinsic resistance to chemo- or radiotherapy, thus representing a substantial concern for cancer treatment. Prostate CSCs’ activity has been shown to be regulated by the transcription factor Signal Transducer and Activator of Transcription 3 (STAT3). Here we investigated the effect of galiellalactone (GL), a direct STAT3 inhibitor, on CSCs derived from prostate cancer patients, on docetaxel-resistant spheres with stem cell characteristics, on CSCs obtained from the DU145 cell line in vitro and on DU145 tumors in vivo. We found that GL significantly reduced the viability of docetaxel-resistant and patient-derived spheres. Moreover, CSCs isolated from DU145 cells were sensitive to low concentrations of GL, and the treatment with GL suppressed their viability and their ability to form colonies and spheres. STAT3 inhibition down regulated transcriptional targets of STAT3 in these cells, indicating STAT3 activity in CSCs. Our results indicate that GL can target the prostate stem cell niche in patient-derived cells, in docetaxel-resistant spheres and in an in vitro model. We conclude that GL represents a promising therapeutic approach for prostate cancer patients, as it reduces the viability of prostate cancer-therapy-resistant cells in both CSCs and non-CSC populations.</p>}},
  author       = {{Canesin, Giacomo and Maggio, Valentina and Palominos, Macarena and Stiehm, Anna and Contreras, Hector R. and Castellón, Enrique A. and Morote, Juan and Paciucci, Rosanna and Maitland, Norman J. and Bjartell, Anders and Hellsten, Rebecka}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{STAT3 inhibition with galiellalactone effectively targets the prostate cancer stem-like cell population}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-70948-5}},
  doi          = {{10.1038/s41598-020-70948-5}},
  volume       = {{10}},
  year         = {{2020}},
}