Anti-glioma Effects of Caffeic Acid Phenethyl Ester and Dasatinib Combination Therapy in an in vivo Rat Glioma Model

Abstract

Background: Caffeic acid phenethyl ester and Dasatinib in combination, when used incongruous proportions and durations, present an antitumor potential for glioma in vitro, suggesting a high therapeutic potential for glioma treatment. Objective: In the present study, we addressed the question whether CAPE and Dasatinib target multiple pathways involved in tumor growth, proliferation and development on an in vivo rat model of glioma. Method: Expression analysis of proteins thought to be mediating proliferation, cell motility, angiogenesis, and invasion was carried out to delineate the antineoplastic action of CAPE and Dasatinib. Results: 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 in group co-administered with CAPE and Dasatinib after glioma induction in comparison to the group induced with glioma only. EGFR and PCNA expression were significantly altered in the co-treated group in comparison with the glioma-induced group. The effects of CAPE and Dasatinib treatment were further evaluated on the AKT pathway by Western blot analysis. The co-treated group showed a significant reduction in the expression of AKT. The histopathological analysis further backed the antiproliferative and anti invasive effects of CAPE and Dasatinib. Conclusion: This study in totality suggests that the combinational therapy remarkably reduces the proliferation of glioma cells in vivo, suggesting that CAPE and Dasatinib therapy could be exploited for the management of gliomas without showing drug-related resistances and side effects, suggesting a high therapeutic potential of the therapy in glioma.