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3 janvier 2017 2 03 /01 /janvier /2017 07:26

Syrosingopine sensitizes cancer cells to killing by metformin.

Benjamin D, et al. Sci Adv. 2016.

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.

PMID 28028542 [PubMed - in process] PMCID PMC5182053

Syrosingopine — A New Rauwolfia Preparation Carl C. Bartels, M.D.† October 15, 1959 N Engl J Med 1959; 261:785-788

RAUWOLFIA preparations have been widely accepted in the treatment of hypertension since they were introduced by Vakil1 in 1949 and Wilkins and his associates2 in 1952.

They are simple to administer and have a wide margin of safety.

Troublesome side effects of depression, lethargy, sedation, nasal congestion, increased appetite, nightmares, headaches and gastrointestinal symptoms have become well recognized. Depression, which is the most serious of these side effects, has reached the point of suicide in some cases. It may develop insidiously even after three years of treatment.

The type and frequency of side effects and the blood-pressure response vary little . . .

ORIGINAL ARTICLE Comparative Observations of Reserpine and Syrosingopine Bertram M. Winer, M.D.†, and Bal M. Sahay, M.D.‡ December 8, 1960 N Engl J Med 1960; 263:1165-1169 Hide Abstract / Article Extract IN animals, syrosingopine, a synthetic derivative of reserpine, has hypotensive activity equivalent to that of reserpine, but markedly less sedative effect.1 In man, syrosingopine has been reported to have hypotensive effects and virtually no side effects when administered orally in doses of 1 to 5 mg. a day.23456 Our studies indicate that syrosingopine does not have hypotensive potency equivalent to that of reserpine when administered orally in human hypertensive subjects. The evidence suggests that in man syrosingopine is either poorly absorbed or inactivated in the gastrointestinal tract. Materials and Methods The effects of orally administered reserpine and syrosingopine were compared . . .

Full :

http://advances.sciencemag.org/content/2/12/e1601756.full

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