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Updated: Dec 11, 2025
Isolation of Stem-like Cells from 3-Dimensional Spheroid Cultures
Published on: December 13, 2019
STAT3 inhibition with galiellalactone effectively targets the prostate cancer stem-like cell population
Giacomo Canesin1,2, Valentina Maggio3, Macarena Palominos4
1Division of Urological Cancers, Department of Translational Medicine, Skåne University Hospital Malmö, Lund University, Malmö, Sweden. giacomo.canesin@gmail.com.
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 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.
Insights
Galiellalactone (GL) effectively targets prostate cancer stem cells (CSCs) and therapy-resistant populations. This STAT3 inhibitor reduces CSC viability and colony formation, offering a promising therapeutic strategy for prostate cancer treatment.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Cancer stem cells (CSCs) drive tumor initiation, progression, and treatment resistance.
- Prostate CSC activity is regulated by Signal Transducer and Activator of Transcription 3 (STAT3).
- STAT3 inhibition is a potential therapeutic strategy for targeting resistant cancer populations.
Purpose of the Study:
- To investigate the effect of galiellalactone (GL), a STAT3 inhibitor, on prostate CSCs.
- To evaluate GL's efficacy in patient-derived CSCs, docetaxel-resistant spheres, and in vitro/in vivo models.
- To determine if GL can overcome chemoresistance in prostate cancer.
Main Methods:
- Treatment of patient-derived CSCs and docetaxel-resistant spheres with GL.
- Assessment of GL's effect on CSC viability, colony formation, and sphere formation in vitro.
- Analysis of STAT3 transcriptional targets following GL treatment.
- Evaluation of GL in DU145 cell line-derived CSCs and in vivo DU145 tumors.
Main Results:
- GL significantly reduced the viability of docetaxel-resistant and patient-derived CSC spheres.
- GL suppressed the viability and self-renewal capacity (colony and sphere formation) of DU145 CSCs.
- STAT3 inhibition by GL downregulated its transcriptional targets, confirming STAT3 activity in CSCs.
- GL demonstrated efficacy in targeting prostate CSCs across various models, including patient-derived and resistant cells.
Conclusions:
- Galiellalactone (GL) effectively targets the prostate cancer stem cell niche.
- GL reduces the viability of both CSCs and non-CSCs, including therapy-resistant populations.
- GL represents a promising therapeutic agent for prostate cancer, particularly for overcoming treatment resistance.
