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

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

Author information

1
Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA, U.S.A.
2
Department of Surgery, Thomas Jefferson University, Philadelphia, PA, U.S.A.
3
Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, PA, U.S.A.
4
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy and ISU Biomedical Research Institute, Division of Health Sciences, Idaho State University, Pocatello, ID, U.S.A.
5
Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA, U.S.A. Alok.Bhushan@jefferson.edu.

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.

KEYWORDS:

Glioblastoma; biochanin A; isoflavone; metabolism; temozolomide

PMID:
30591440
DOI:
10.21873/anticanres.13079
[Indexed for MEDLINE]

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