P-105 - Effect of a novel biscumarin derivative on human melanoma cells: Regulation of cell survival, proliferation, migration and kinases

Abstract

We have investigated the effects of a newly synthesized biscumarin derivative on cell survival, proliferation, migration and signal transduction pathways in the human metastatic melanoma cells A375. Among the modulated pathways of cell survival and tumor suppression we found highly significant effects of this novel synthetic derivative on TOR (Target of Rapamycin), Checkpoint Kinase 2 (Chk- 2), Tumor Suppressor Protein Kinase p53 ( P53), Additionally the compound was found to modulate a number of pathways of cell proliferation with varying degree of efficacy. We have shown that biscumarin derivative induced activation of Epidermal Growth Factor Receptor (EGFR), Focal Adhesion Kinase (FAK), cAMP response Element-Binding Protein (CREB), Glycogen Synthase Kinase (GSK3 α/f3) and f3 –catenin: this effect may be at thebases of observed motility inhibition of melanoma cell caused by the compound. We have shown that the biscumarin derivative diminish phosphorylation of CHK-2 protein, TOR and P53 an event that is likely be the basis of observed inhibition of melanoma cell survival and tumor growth. Inhibition of cell survival and growth possibly due to the deminish phosphorylation of the chk-2 kinase on Threonine: T68, of TOR on Serine: S2448 of P53 on Serine: S392.