2-4-3--5--tetrahydroxystilbene and Prostatic-Neoplasms

The proto-oncogene receptor tyrosine kinase c-Met encodes the high-affinity receptor for hepatocyte growth factor (HGF). Dysregulation of the HGF-c-Met pathway plays a significant oncogenic role in many tumors. Overexpression of c-Met is a prognostic indicator for some transitional cell carcinomas. Extra-virgin olive oil (EVOO) provides a variety of minor phenolic compounds with beneficial properties. (-)-Oleocanthal (1) is a naturally occurring minor secoiridoid isolated from EVOO, which showed potent anti-inflammatory activity via its ability to inhibit COX-1 and COX-2. It altered the structure of neurotoxic proteins believed to contribute to the debilitating effects of Alzheimer's disease. Computer-Assisted Molecular Design (CAMD) identified 1 as a potential virtual c-Met inhibitor hit. Oleocanthal inhibited the proliferation, migration, and invasion of the epithelial human breast and prostate cancer cell lines MCF7, MDA-MB-231, and PC-3, respectively, with an IC (50) range of 10-20 µM, and demonstrated anti-angiogenic activity via downregulating the expression of the microvessel density marker CD31 in endothelial colony forming cells with an IC (50) of 4.4 µM. It inhibited the phosphorylation of c-Met kinase IN VITRO in the Z'-LYTE™ assay, with an IC (50) value of 4.8 µM. (-)-Oleocanthal and EVOO can have potential therapeutic use for the control of c-Met-dependent malignancies.

Topics: Adenosine Triphosphate; Aldehydes; Angiogenesis Inhibitors; Antineoplastic Agents, Phytogenic; Binding Sites; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cyclopentane Monoterpenes; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Humans; Inhibitory Concentration 50; Male; Models, Molecular; Neoplasm Invasiveness; Neovascularization, Pathologic; Olive Oil; Phenols; Plant Oils; Platelet Endothelial Cell Adhesion Molecule-1; Prostatic Neoplasms; Protein Kinases; Proto-Oncogene Mas; Proto-Oncogene Proteins c-met