Abstract
Cancer stem cells (CSCs), including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in the prevention and treatment of many cancers. Berberis libanotica Ehrenb (BLE) is a plant rich in alkaloids which may possess anti-cancer activity and a high potential for eliminating CSCs. We tested the effect of BLE on prostate cancer cells and our data indicated that this extract induced significant reduction in cell viability and inhibited the proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1) in a dose- and time-dependent manner. BLE extract induced a perturbation of the cell cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death, characterized by the production of high levels of reactive oxidative species (ROS). Inhibition of cellular migration and invasion was also achieved upon treatment with BLE extract, suggesting a role in inhibiting metastasis. Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D sphere-formation assay to enrich for a population of cancer stem/progenitor cells. Our results showed a significant reduction in sphere formation ability. Three rounds of treatment with BLE extract were sufficient to eradicate the self-renewal ability of highly resistant CSCs. In conclusion, our results suggest a high therapeutic potential of BLE extract in targeting prostate cancer and its CSCs.
Highlights
Prostate cancer (PC) is the most commonly diagnosed noncutaneous malignancy and the third most common cause of cancer mortality in the Western male population [1,2]
After 72 h of treatment, the inhibitory effect commenced at low concentrations and significantly inhibited proliferation by 50% when PC cells were grown in media supplied with 30 mg/ml of Berberis libanotica Ehrenb (BLE) extract
Berberis libanotica extract exhibited anti-neoplastic effects by reducing the viability and proliferation of three PC cell lines in a time- and dose-dependent manner, whereby the 22RV-1 cell line showed a higher sensitivity to treatment than the other two cell lines (PC3 and DU145)
Summary
Prostate cancer (PC) is the most commonly diagnosed noncutaneous malignancy and the third most common cause of cancer mortality in the Western male population [1,2]. Prostate cancer stem cells (CSCs) share properties with normal stem cells as they tend to express high levels of: aldehyde dehydrogenase (ALDH) - a detoxifying enzyme - [3], multidrug resistance (MDR) efflux pumps and ABC transporters [4,5,6]. These defensive strategies render conventional therapy ineffective, due to the presence of fast proliferative cells in the tumor bulk and a great potential for sparing the putative cancer stem/progenitor cells [7]. Following ADT, cancer stem cells may frequently manage to repopulate the tumor mass with androgen-independent PC, which is an aggressively metastatic and lethal form of PC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
