Syrosingopine sensitizes cancer cells to killing by metformin | Zendy

Don Benjamin | Zendy; Marco Colombi | Zendy; Sravanth K. Hindupur | Zendy; Charles Betz | Zendy; Heidi A. Lane | Zendy; Mahmoud ElShemerly | Zendy; Min Lu | Zendy; Luca Quagliata | Zendy; Luigi Terracciano | Zendy; Suzette Moes | Zendy; Timothy Sharpe | Zendy; Aleksandra WodnarFilipowicz | Zendy; Christoph Moroni | Zendy; Michael N. Hall | Zendy

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Syrosingopine sensitizes cancer cells to killing by metformin

Author(s) -

Don Benjamin,

Marco Colombi,

Sravanth K. Hindupur,

Charles Betz,

Heidi A. Lane,

Mahmoud ElShemerly,

Min Lu,

Luca Quagliata,

Luigi Terracciano,

Suzette Moes,

Timothy Sharpe,

Aleksandra WodnarFilipowicz,

Christoph Moroni,

Michael N. Hall

Publication year - 2016

Publication title -

science advances

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.928

H-Index - 146

ISSN - 2375-2548

DOI - 10.1126/sciadv.1601756

Subject(s) - metformin , cancer , lethality , synthetic lethality , medicine , cancer cell , pharmacology , cancer research , biology , toxicology , dna repair , biochemistry , gene , insulin

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 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

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