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PKM2 activation sensitizes cancer cells to growth inhibition by 2-deoxy-D-glucose.
PKM2 activation sensitizes cancer cells to growth inhibition by 2-deoxy-D-glucose. Oncotarget Tee, S. S., Park, J. M., Hurd, R. E., Brimacombe, K. R., Boxer, M. B., Massoud, T. F., Rutt, B. K., Spielman, D. M. 2017; 8 (53): 90959-90968Abstract
Cancer metabolism has emerged as an increasingly attractive target for interfering with tumor growth. Small molecule activators of pyruvate kinase isozyme M2 (PKM2) suppress tumor formation but have an unknown effect on established tumors. We demonstrate that TEPP-46, a PKM2 activator, results in increased glucose consumption, providing the rationale for combining PKM2 activators with the toxic glucose analog, 2-deoxy-D-glucose (2-DG). Combination treatment resulted in reduced viability of a range of cell lines in standard cell culture conditions at concentrations of drugs that had no effect when used alone. This effect was replicated in vivo on established subcutaneous tumors. We further demonstrated the ability to detect acute metabolic differences in combination treatment using hyperpolarized magnetic resonance spectroscopy (MRS). Combination treated tumors displayed a higher pyruvate to lactate 13C-label exchange 2 hr post-treatment. This ability to assess the effect of drugs non-invasively may accelerate the implementation and clinical translation of drugs that target cancer metabolism.
View details for DOI 10.18632/oncotarget.19630
View details for PubMedID 29207616
View details for PubMedCentralID PMC5710897