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

Anticancer Res. 2019 Jan;39(1):57-66. doi: 10.21873/anticanres.13079.


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.

Keywords: Glioblastoma; biochanin A; isoflavone; metabolism; temozolomide.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genistein / pharmacology*
  • Glioblastoma / drug therapy*
  • Humans
  • Mice
  • Mitochondria / drug effects
  • Signal Transduction / drug effects
  • Temozolomide / pharmacology*
  • Xenograft Model Antitumor Assays


  • Genistein
  • biochanin A
  • Temozolomide