Syrosingopine sensitizes cancer cells to killing by metformin
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 inhi...
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| Veröffentlicht in: | Science advances 2016-12, Vol.2 (12), p.e1601756-e1601756 |
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| creator | Benjamin, Don Colombi, Marco Hindupur, Sravanth K Betz, Charles Lane, Heidi A El-Shemerly, Mahmoud Y M Lu, Min Quagliata, Luca Terracciano, Luigi Moes, Suzette Sharpe, Timothy Wodnar-Filipowicz, Aleksandra Moroni, Christoph Hall, Michael N |
| description | 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. |
| doi_str_mv | 10.1126/sciadv.1601756 |
| format | Article |
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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. 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| subjects | Cancer SciAdv r-articles |
| title | Syrosingopine sensitizes cancer cells to killing by metformin |
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