Potential Synergism of Caffeic Acid Phenethyl Ester and Dasatinib in C6 Glioma Cell Model: Adumbrating the Molecular Mechanism

Abstract

1.1 Background: Gliomas are one of the most invasive, highly recurrent, heterogeneous cancers resistant to most of the current treatment regimes and hence almost incurable. CAPE and Dasatinib when used in a congruous combination and durations, present an antitumor potential for glioma. 1.2 Objective: CAPE and Dasatinib in combination have been shown to inhibit proliferation and induce apoptosis in C6 glioma cells. However, the signaling pathway of their antiproliferative and apoptotic effects remains unknown. In this study, the antiproliferative effects of combination treatment on C6 glioma cells were investigated. 1.3 Methods: Expression analysis of proteins thought to be mediating proliferation, cell motility, angiogenesis, and invasion was carried out to delineate the molecular mechanism entailing antineoplastic action of CAPE and Dasatinib. 1.4 Results: Co-treatment induces a change in cellular and nuclear morphology followed by apoptosis and a significant decrease in the activity of catalase and MMP-2, Pro-MMP 2, MMP-9 and Pro-MMP 9 in C6 glioma cells. Moreover, CAPE and Dasatinib modulate the expression of proteins having potential interactive crosstalk with major oncogenic pathways involved in glioma progression. Our results showed that combination treatment modulates the expression of p53, ERK1/2, and AKT in C6 glioma cells. p53, EGFR and PCNA transcript expressions were attuned in co-treated C6 cells. 1.5 Conclusion: Importantly, antineoplastic effects of CAPE and Dasatinib were far greater than those afforded by treatment with a single drug. Together these drugs reduce glioma proliferation and invasion felicitously implying that combination treatment could be a useful therapy for treatment of glioma.