Abstract
Numerous data suggest that an increase of cancer stem cells (CSCs) in tumor mass can be the reason for failure of conventional therapies because of their resistance. CD44+/CD24− cells are a putative cancer stem cells subpopulation in prostate cancer. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is an activator of apoptosis in tumor cells. However, some tumors are TRAIL-resistant. Cancer cells can be re-sensitized to TRAIL induced apoptosis by a combination of TRAIL and taxanes. The aim of this work was to analyze the enhancement of the anticancer effect of TRAIL by paclitaxel, cabazitaxel and docetaxel in the whole population of PC3 and DU145 prostate cancer cells, but also in CD44+/CD24− prostate cancer stem cells. We examined the apoptotic effect of TRAIL and taxanes using flow cytometry and Annexin-V-PE staining. The co-treatment with taxanes and TRAIL enhanced significantly the apoptosis in CD44+/CD24− cells only in PC3 cell line but not in DU145 cells. We discovered also that taxanes can increase the expression of death receptor TRAIL-R2 in PC3 prostate cancer cells. The results of our study show that treatment with paclitaxel, cabazitaxel and docetaxel is able to enhance the apoptosis induced by TRAIL even in prostate cancer stem cells.
Highlights
Prostate cancer represents one of the most prevalent cancers diagnosed in men and remains the second leading cause of cancer related deaths in Europe and the United States [1,2,3].In the last decades, prostate cancer research focused on the hypothesis concerning cancer stem cells (CSCs) and their role in the development of prostate cancer
Studies identified CD44+/CD24− prostate cancer cells in established prostate cancer cell lines and showed that these subpopulations were more invasive, tumorigenic and were able to differentiate into mature tumor cells expressing highly aggressive phenotype [8,15,16,17]
The aim of this study was to prove the hypothesis that cancer stem cells (CSCs) present in the population of prostate cancer cells can be responsible for the increased resistance of the tumor for the natural immune system anticancer agents such as ligand TRAIL
Summary
Prostate cancer represents one of the most prevalent cancers diagnosed in men and remains the second leading cause of cancer related deaths in Europe and the United States [1,2,3].In the last decades, prostate cancer research focused on the hypothesis concerning cancer stem cells (CSCs) and their role in the development of prostate cancer. The ideal combination which could result in distinction of cancer stem cells have not been found yet, because of prostate cancer genetic heterogeneity. In 2006, Patrawala et al [14] demonstrated that CD44+ prostate cancer cells have increased metastatic potential, form colonies in soft agar and tumors in NOD/SCID mice. Afterwards, Hurt et al [9] discovered that CD44+/CD24− prostate cancer cells have the unique ability to grow as nonadherent spheres in serum replacement medium and have the potential to form tumors in NOD/SCID mice. This marker combination let them identify putative prostate cancer stem cells. Studies identified CD44+/CD24− prostate cancer cells in established prostate cancer cell lines and showed that these subpopulations were more invasive, tumorigenic and were able to differentiate into mature tumor cells expressing highly aggressive phenotype [8,15,16,17]
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