Syrosingopine sensitizes cancer cells to killing by metformin.

Autor:	Benjamin D; Biozentrum, University of Basel, 4056 Basel, Switzerland., Colombi M; Biozentrum, University of Basel, 4056 Basel, Switzerland., Hindupur SK; Biozentrum, University of Basel, 4056 Basel, Switzerland., Betz C; Biozentrum, University of Basel, 4056 Basel, Switzerland., Lane HA; Basilea Pharmaceutica International Ltd., Basel, Switzerland., El-Shemerly MY; Basilea Pharmaceutica International Ltd., Basel, Switzerland., Lu M; Institute for Medical Microbiology, University of Basel, 4003 Basel, Switzerland., Quagliata L; Molecular Pathology, University Hospital Basel, 4003 Basel, Switzerland., Terracciano L; Molecular Pathology, University Hospital Basel, 4003 Basel, Switzerland., Moes S; Biozentrum, University of Basel, 4056 Basel, Switzerland., Sharpe T; Biozentrum, University of Basel, 4056 Basel, Switzerland., Wodnar-Filipowicz A; Stem Cell Center of Competence, University of Basel, 4056 Basel, Switzerland., Moroni C; Biozentrum, University of Basel, 4056 Basel, Switzerland., Hall MN; Biozentrum, University of Basel, 4056 Basel, Switzerland.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2016 Dec 23; Vol. 2 (12), pp. e1601756. Date of Electronic Publication: 2016 Dec 23 (Print Publication: 2016).
DOI:	10.1126/sciadv.1601756
Abstrakt:	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.
Databáze:	MEDLINE
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