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Syrosingopine sensitizes cancer cells to killing by metformin.

ABSTRACT: We report that the anticancer activity of the widely used diabetic drug metformin is strongly potentiated by syrosingopine. Synthetic lethality elicited by combining the two drugs is synergistic and specific to transformed cells. This effect is unrelated to syrosingopine's known role as an inhibitor of the vesicular monoamine transporters. Syrosingopine binds to the glycolytic enzyme ?-enolase in vitro, and the expression of the ?-enolase isoform correlates with nonresponsiveness to the drug combination. Syrosingopine sensitized cancer cells to metformin and its more potent derivative phenformin far below the individual toxic threshold of each compound. Thus, combining syrosingopine and codrugs is a promising therapeutic strategy for clinical application for the treatment of cancer.

SUBMITTER: Benjamin D

PROVIDER: S-EPMC5182053 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Syrosingopine sensitizes cancer cells to killing by metformin.

Benjamin Don D Colombi Marco M Hindupur Sravanth K SK Betz Charles C Lane Heidi A HA El-Shemerly Mahmoud Y M MY Lu Min M Quagliata Luca L Terracciano Luigi L Moes Suzette S Sharpe Timothy T Wodnar-Filipowicz Aleksandra A Moroni Christoph C Hall Michael N MN

Science advances 20161223 12

We report that the anticancer activity of the widely used diabetic drug metformin is strongly potentiated by syrosingopine. Synthetic lethality elicited by combining the two drugs is synergistic and specific to transformed cells. This effect is unrelated to syrosingopine's known role as an inhibitor of the vesicular monoamine transporters. Syrosingopine binds to the glycolytic enzyme α-enolase in vitro, and the expression of the γ-enolase isoform correlates with nonresponsiveness to the drug com ...[more]

PMID: 28028542

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