Berberis libanotica ehrenb extract shows anti-neoplastic effects on prostate cancer stem/progenitor cells
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Public Library of Science
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. Copyright: © 2014 El-Merahbi et al.
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Antineoplastic agents, Apoptosis, Berberis, Cell cycle checkpoints, Cell line, tumor, Cell proliferation, Cell survival, Dose-response relationship, drug, Flow cytometry, Gene expression regulation, neoplastic, Homeodomain proteins, Humans, Male, Neoplastic stem cells, Octamer transcription factor-3, Plant extracts, Plant roots, Prostatic neoplasms, Reactive oxygen species, Reverse transcriptase polymerase chain reaction, Soxb1 transcription factors, Antineoplastic agent, Berberis libanotica extract, Plant extract, Reactive oxygen metabolite, Unclassified drug, Homeodomain protein, Nanog protein, human, Octamer transcription factor 4, Pou5f1 protein, human, Sox2 protein, human, Transcription factor sox, Antineoplastic activity, Article, Berberis libanotica, Cancer inhibition, Cell cycle g0 phase, Cell renewal, Cell viability, Concentration response, Controlled study, Drug cytotoxicity, G1 phase cell cycle checkpoint, Human, Human cell, Mitosis inhibition, Oxidative stress, Prostate cancer, Prostate cancer cell line, Target cell, Tumor invasion, Cancer stem cell, Cell cycle checkpoint, Chemistry, Dose response, Drug effects, Gene expression regulation, Genetics, Metabolism, Pathology, Plant root, Prostate tumor, Reverse transcription polymerase chain reaction, Tumor cell line