PloS one, 2014-05, Vol.9 (5), p.e97622-e97622
2014
Details
- Autor(en) / Beteiligte
- Titel
- Olive phenolics as c-Met inhibitors: (-)-Oleocanthal attenuates cell proliferation, invasiveness, and tumor growth in breast cancer models
- Ist Teil von
- PloS one, 2014-05, Vol.9 (5), p.e97622-e97622
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Dysregulation of the Hepatocyte growth factor (HGF)/c-Met signaling axis upregulates diverse tumor cell functions, including cell proliferation, survival, scattering and motility, epithelial-to-mesenchymal transition (EMT), angiogenesis, invasion, and metastasis. (-)-Oleocanthal is a naturally occurring secoiridoid from extra-virgin olive oil, which showed antiproliferative and antimigratory activity against different cancer cell lines. The aim of this study was to characterize the intracellular mechanisms involved in mediating the anticancer effects of (-)-oleocanthal treatment and the potential involvement of c-Met receptor signaling components in breast cancer. Results showed that (-)-oleocanthal inhibits the growth of human breast cancer cell lines MDA-MB-231, MCF-7 and BT-474 while similar treatment doses were found to have no effect on normal human MCF10A cell growth. In addition, (-)-oleocanthal treatment caused a dose-dependent inhibition of HGF-induced cell migration, invasion and G1/S cell cycle progression in breast cancer cell lines. Moreover, (-)-oleocanthal treatment effects were found to be mediated via inhibition of HGF-induced c-Met activation and its downstream mitogenic signaling pathways. This growth inhibitory effect is associated with blockade of EMT and reduction in cellular motility. Further results from in vivo studies showed that (-)-oleocanthal treatment suppressed tumor cell growth in an orthotopic model of breast cancer in athymic nude mice. Collectively, the findings of this study suggest that (-)-oleocanthal is a promising dietary supplement lead with potential for therapeutic use to control malignancies with aberrant c-Met activity.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0097622Titel-ID: cdi_plos_journals_1526931542
- Format
- –
- Schlagworte
- Aldehydes - pharmacology, Angiogenesis, Animal models, Animals, Anticancer properties, Antineoplastic Agents - pharmacology, Apoptosis, Apoptosis - drug effects, Biology and Life Sciences, Biotechnology, Breast cancer, Breast Neoplasms - pathology, c-Met protein, Cancer, Cancer therapies, Cell cycle, Cell Cycle - drug effects, Cell growth, Cell Line, Tumor, Cell migration, Cell proliferation, Cell Proliferation - drug effects, Cell survival, Diet, Dietary supplements, Downstream effects, Epidermal growth factor, Epithelial-Mesenchymal Transition - drug effects, Female, Hepatocyte growth factor, Hepatocyte Growth Factor - pharmacology, Humans, Immunoglobulins, In vivo methods and tests, Inhibition, Intracellular Space - drug effects, Intracellular Space - metabolism, Invasiveness, Kinases, Medicine and Health Sciences, Mesenchyme, Metastases, Metastasis, Mice, Mitogen-Activated Protein Kinases - metabolism, Neoplasm Invasiveness, Oils & fats, Olea - chemistry, Olive oil, Penicillin, Pharmaceutical sciences, Pharmacy, Phenols - pharmacology, Phosphorylation - drug effects, Physical Sciences, Protein Kinase Inhibitors - pharmacology, Proto-Oncogene Proteins c-akt - metabolism, Proto-Oncogene Proteins c-met - antagonists & inhibitors, Signal Transduction - drug effects, Signaling, Stem cells, Tumor cell lines, Xenograft Model Antitumor Assays