Combination of Biochanin A and Temozolomide Impairs Tumor Growth by Modulating Cell Metabolism in Glioblastoma Multiforme

Abstract

Background/Aim: Several epidemiological studies have reported the chemopreventive potential of biochanin A, in cancer development and progression. We investigated the anticancer potential of combination of biochanin A and temozolomide against U-87 MG and T98 G [glioblastoma multiforme (GBM)] cells. Materials and Methods: We evaluated the effect of biochanin A and temozolomide treatment on cell viability, expression of survival proteins, cell cycle, cell metabolism and mitochondrial function. Results: Enhanced inhibitory effects of the combination treatment were observed on cell viability, expression of cell survival proteins EGFR, p-ERK, p-AKT, c-myc and MT-MMP1, and increased expression of the tumor suppressor, p-p53. Combination treatment also induced arrest in the G₁ phase of the cell cycle. A shift in the metabolic phenotype of cells from glycolytic to oxidative phosphorylation was observed on combination treatment and the permeabilized cells showed a significant impairment in complex IV activity. Conclusion: Biochanin A significantly enhanced the anticancer efficacy of temozolomide in GBM cells.