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Syrosingopine Sensitizes Cancer Cells to Killing by Metformin

Don Benjamin, Marco Colombi, Sravanth K Hindupur, Charles Betz, Heidi A Lane, Mahmoud Y M El-Shemerly, Min Lu, Luca Quagliata, Luigi Terracciano, Suzette Moes, Timothy Sharpe, Aleksandra Wodnar-Filipowicz, etc.

Sci Adv. 2016 Dec 23;2(12):e1601756.

PMID: 28028542

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 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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP84366 Syrosingopine Syrosingopine 84-36-6 Price
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