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Updated: Jun 24, 2026

Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
Published on: March 14, 2014
Inhibition of c-FLIP alongside TRAIL treatment suppresses prostate cancer stem cell activity
Daniel J Turnham1,2, Rhiannon French3, Fiona M Frame4
1European Cancer Stem Cell Research Institute, Cardiff University, Hadyn Ellis Building, Maindy Road, Cathays, Cardiff, CF24 4HQ, UK. daniel.turnham@uwe.ac.uk.
Background:
Prostate cancer is a leading cause of cancer-associated death in men worldwide. Inhibition of the Cellular FLICE-like Inhibitory Protein (cFLIP), which is overexpressed in prostate cancer, alongside TRAIL treatment can trigger apoptosis and suppress cancer stem cell (CSC) activity in different cancer types but has not been fully explored in prostate cancer.
Methods:
Established and primary prostate cancer lines were treated with the cFLIP inhibitor, OH14, in combination with recombinant TRAIL to investigate changes in viability and colony forming potential. Patient-derived xenograft (PDX) tumour cells were treated ex vivo and re-transplanted into mice in limiting dilution assays. Docetaxel resistant PC-3 cells were also treated with OH14 +/- docetaxel, while PDX tumours were treated in vivo with this combination.
Results:
Combined OH14 and TRAIL treatment induced a potent apoptotic response in prostate cancer cells, significantly reducing viability and CSC activity compared to single agents. OH14 also sensitised tumour cells to docetaxel both in vitro and in vivo.
Conclusions:
Inhibition of cFLIP in combination with either TRAIL or docetaxel has the potential to be used as a novel therapeutic approach to provide more potent, long-lasting benefits to men with prostate cancer.
Insights
Inhibiting Cellular FLICE-like Inhibitory Protein (cFLIP) with OH14 and TRAIL or docetaxel shows promise for treating prostate cancer. This combination therapy effectively reduces cancer cell viability and stem cell activity.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Prostate cancer remains a significant cause of male cancer mortality globally.
- Cellular FLICE-like Inhibitory Protein (cFLIP) overexpression is noted in prostate cancer.
- Targeting cFLIP with TRAIL can induce apoptosis and reduce cancer stem cell (CSC) activity in various cancers, but its role in prostate cancer requires further investigation.
Purpose of the Study:
- To investigate the efficacy of inhibiting cFLIP in combination with TRAIL or docetaxel in prostate cancer.
- To evaluate the impact on cancer cell viability, colony formation, and CSC activity.
Main Methods:
- Prostate cancer cell lines and patient-derived xenografts (PDX) were treated with a cFLIP inhibitor (OH14) and/or TRAIL.
- Docetaxel resistance models were utilized, with treatments including OH14 +/- docetaxel.
- In vitro and in vivo assays assessed viability, colony formation, and CSC activity.
Main Results:
- Combined OH14 and TRAIL treatment significantly enhanced apoptosis and reduced viability and CSC activity in prostate cancer cells.
- OH14 sensitized prostate cancer cells to docetaxel, both in vitro and in vivo.
- Patient-derived xenograft (PDX) models demonstrated the efficacy of combination therapies.
Conclusions:
- Inhibition of cFLIP, in combination with TRAIL or docetaxel, presents a potential novel therapeutic strategy for prostate cancer.
- This approach may offer more potent and durable therapeutic benefits for patients.
- Targeting cFLIP could overcome docetaxel resistance in prostate cancer.
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