Individual and Combined Treatments with Methylated Resveratrol Analogue DMU-214 and Gefitinib Inhibit Tongue Cancer Cells Growth via Apoptosis Induction and EGFR Inhibition

Abstract

The methylated resveratrol analogue 3′-hydroxy-3,4,5,4′-tetramethoxystilbene (DMU-214) has been revealed to exert the anti-cancer activity by a block of the cell cycle at the G2/M phase, apoptosis induction, and metastasis inhibition. These biological events may be involved in crosstalk with the epidermal growth factor receptor (EGFR), which belongs to the ErbB family of receptor tyrosine kinases. Several cancer therapeutic approaches employ small molecules capable of inhibiting tyrosine kinases (e.g., gefitinib). According to more recent reports, combining gefitinib with chemotherapeutics, such as cisplatin, seems to be more effective than monotherapy. The present study aimed to assess the molecular mechanism of the potential anti-proliferative activity of individual and combined treatments with DMU-214 and gefitinib in SCC-25 and CAL-27 human tongue cancer cell lines. We showed for the first time the anti-cancer effects of DMU-214, gefitinib, and their combination in tongue cancer cells triggered via cell cycle arrest, apoptosis induction, and inhibition of the EGFR signaling pathway. The anti-proliferative effects of DMU-214 and gefitinib are also suggested to be related to the EGFR and EGFRP (phosphorylated epidermal growth factor receptor) expression status since we found significantly weaker cytotoxic activity of the compounds tested in SCC-25 cells, which overexpressed EGFR and EGFRP proteins.