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Syrosingopine sensitizes cancer cells to killing by metformin

Benjamin, Don and Colombi, Marco and Hindupur, Sravanth K. and Betz, Charles and Lane, Heidi A. and El-Shemerly, Mahmoud Y. M. and Lu, Min and Quagliata, Luca and Terracciano, Luigi and Moes, Suzette and Sharpe, Timothy and Wodnar-Filipowicz, Aleksandra and Moroni, Christoph and Hall, Michael N.. (2016) Syrosingopine sensitizes cancer cells to killing by metformin. Science Advances, 2 (12). e1601756.

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association for the Advancement of Science
e-ISSN:2375-2548
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:08 Nov 2017 13:29
Deposited On:25 Oct 2017 13:23

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