Role of p38-mitogen-activated protein kinase in modulation of the response to therapy in FaDu Human pharyngeal carcinoma cell

Although cisplatin (CisPt) is used in treating head and neck squamous cell carcinomas (HNSCC), little is known about the cellular mechanisms triggered. We examined the morphological and functional changes in HNSCC cells when natural compounds such as resveratrol (RSV) are added to CisPt treatment of FaDu human pharyngeal carcinoma cell line. In addition, we analyzed the effects of CisPt and/or RSV treatments on cell proliferation and evaluated the ability to modulate the activation of p38 Mitogen-Activated Protein Kinase (p38MAPK). Moreover, we explored whether activation of p38MAPK is associated with p53 phosphorylation status in FaDu cells using SB203580 specific p38MAPK inhibitor. Proliferation vs. cytotoxicity induced by CisPt and/or RSV treatments in FaDu cells were studied using MTS colorimetric assay and evaluating cell viability. Whereas the activation of p38MAPK could be specific to HNSCC therapy, we investigated the phosphorylation status of p38 and p53 proteins by ELISA assays, using antibodies that recognize their dual forms (the active, phosphorylated and the total one). The obtained data showed that RSV enhanced the cytotoxic effect of CisPt in FaDu cells, having a synergic effect and the ability to promote p53 phosphorylation, suggesting a possible link between the p38MAPK and p53 activation pathways.