Alkaloids derived from genus Veratrum and Peganum of Mongolian origin as multidrug resistance inhibitors of cancer cells

Alkaloids comprise one of the largest groups of plant secondary metabolites including vinca alkaloids. The ability of six alkaloids from Veratrum lobelianum, one from Veratrum nigrum and three from Peganum nigellastrum to modify transport activity of MDR1 was studied. Flow-cytometry in a multidrug-resistant human MDR1-gene-transfected mouse lymphoma cells (L5178Y) was applied. The inhibition of multidrug resistance was investigated by measuring the accumulation of rhodamine-123 in cancer cells.Veralosinine and veranigrine were the most effective resistance modifiers. In a checkerboard method veralosinine and veranigrine enhanced the antiproliferative effects of doxorubicin on MDR cells in combination. The structure–activity relationships were discussed.

Graphical AbstractVeralosinine and veranigrine were the most effective resistance modifiers. In a checkerboard method veralosinine and veranigrine enhanced the antiproliferative effects of doxorubicin on MDR cells in combination.Figure optionsDownload full-size imageDownload as PowerPoint slide