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Natural products against cancer migration
The project will involve measuring the effect of plant extracts on viability, cell cycle, ability to induce apoptosis and intracellular red-ox status of human and rat melanoma cells. RT-PCR in parallel with 2D migratory inhibition will be used to unveil mechanisms of action of the active natural products targeting in particular CXCR4, a known player in motility, and MAP4K4 which was found to be mediated through c-Jun N-terminal kinase, independent of AP1 activation and downstream transcription. Plant extracts active in this model will be fractionated and a bioguided isolation of their principles performed. At this stage, keratinocytes will be used as controls for specificity of the anticancer activities. For lead molecules, combination studies with established anticancer drugs will be run and the synergistic or antagonistic effects measured using multiple drug dose-effect calculations using the Median Effect method.
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