TY - JOUR
T1 - Berberis libanotica ehrenb extract shows anti-neoplastic effects on prostate cancer stem/progenitor cells
AU - El-Merahbi, Rabih
AU - Liu, Yen Nien
AU - Eid, Assaad
AU - Daoud, Georges
AU - Hosry, Leina
AU - Monzer, Alissar
AU - Mouhieddine, Tarek H.
AU - Hamade, Aline
AU - Najjar, Fadia
AU - Abou-Kheir, Wassim
N1 - Funding Information:
We would like to thank all the members of the Abou-Kheir's Laboratory for their help on this work. We would like to thank Dr. Kathleen Kelly for her generous gift of the cells used in this study. This research was partly supported by funding from the Medical Practice Plan-MPP (AUB-FM) and the Lebanese National Council for Scientific Research (CNRS).
Publisher Copyright:
© 2014 El-Merahbi et al.
PY - 2014/11/7
Y1 - 2014/11/7
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0112453
DO - 10.1371/journal.pone.0112453
M3 - Article
C2 - 25380390
AN - SCOPUS:84911397133
SN - 1932-6203
VL - 9
JO - PLoS One
JF - PLoS One
IS - 11
M1 - e112453
ER -