PKM2 activation sensitizes cancer cells to growth inhibition by 2-deoxy-D-glucose.

ABSTRACT: 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 h

SUBMITTER: Tee SS 

PROVIDER: S-EPMC5710897 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature