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

被引:28
作者
Desai, Vilas [1 ]
Jain, Aditi [2 ]
Shaghaghi, Hoora [3 ,4 ]
Summer, Ross [3 ,4 ]
Lai, James C. K. [5 ,6 ]
Bhushan, Alok [1 ]
机构
[1] Thomas Jefferson Univ, Jefferson Coll Pharm, Dept Pharmaceut Sci, Philadelphia, PA 19107 USA
[2] Thomas Jefferson Univ, Dept Surg, Philadelphia, PA 19107 USA
[3] Thomas Jefferson Univ, Ctr Translat Med, Philadelphia, PA 19107 USA
[4] Thomas Jefferson Univ, Jane & Leonard Korman Lung Ctr, Philadelphia, PA 19107 USA
[5] Idaho State Univ, Coll Pharm, Dept Biomed & Pharmaceut Sci, Pocatello, ID 83209 USA
[6] Idaho State Univ, Div Hlth Sci, ISU Biomed Res Inst, Pocatello, ID 83209 USA
关键词
Glioblastoma; biochanin A; temozolomide; isoflavone; metabolism; WILD-TYPE EGFR; CANCER PREVENTION; RADIATION; GENISTEIN; P53; EPIDEMIOLOGY; IRRADIATION; INHIBITION; ACTIVATION; RESISTANCE;
D O I
10.21873/anticanres.13079
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 G(1) 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.
引用
收藏
页码:57 / 66
页数:10
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