Abstract 243: Differential effects of combination treatment of biochanin A and statins on glioblastoma multiforme cell proliferation and cell metabolism

Abstract

Abstract Glioblastoma Multiforme (GBM) is a deadly brain cancer and represents the most common central nervous system (CNS) tumors in adults. Although GBM does not metastasize, its aggressive growth and invasive nature are responsible for poor patient prognosis. The current standard therapy for newly diagnosed GBM patients involves surgical resection, followed by radiation and chemotherapy with Temozolomide. However, its rapid rate of infiltration into normal brain tissue ultimately renders the therapy ineffective. Epidemiological studies on dietary isoflavones (e.g., genistein, biochanin A) have shown their anti-cancer potential in different cancers. Though primarily used in management of hyperlipidemia and cardiovascular diseases, statins are known to exert anti-proliferative effects. We therefore hypothesized that a combination treatment of biochanin A & statins (e.g., Atorvastatin, Lovastatin, Simvastatin, Fluvastatin and Pravastatin) exerts enhanced anticancer effects on GBM U-87 MG and T98 G cells. Our studies showed statins induced differential effects on viability of GBM cells in combination with biochanin A, with U-87 MG being more susceptible than T98 G cells. The combination treatment of biochanin A and atorvastatin also decreased invasion in U-87 MG cells. Additionally, cell metabolism studies using seahorse XFp analyzer showed a switch in their metabolic phenotype with an increase in mitochondrial respiration and a decrease in glycolytic activity with the combination treatment. We also performed metabolite extraction on GBM cells for a global unbiased profiling of metabolites using a single extraction procedure and dual separation analysis by LCMS. A differential analysis of alternative GBM treatment indicated statistically significant changes in carbohydrate and amino acid metabolism as well as alterations to various degradation pathway intermediates. Together, the combination treatment-induced effects on GBM cell lines are differential and our results may have potential implications in developing combination therapies with biochanin A in vivo and support the design of new and better therapies for the treatment of a lethal cancer like GBM. Citation Format: Vilas S. Desai, Eric Buchhalter, Max Cabanzo, Arushi Tiwari, Gagan Kaushal, James C. Lai, Alok Bhushan. Differential effects of combination treatment of biochanin A and statins on glioblastoma multiforme cell proliferation and cell metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 243.