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  • Title: Synergism of three-drug combinations of sanguinarine and other plant secondary metabolites with digitonin and doxorubicin in multi-drug resistant cancer cells.
    Author: Eid SY, El-Readi MZ, Wink M.
    Journal: Phytomedicine; 2012 Nov 15; 19(14):1288-97. PubMed ID: 23146422.
    Abstract:
    We determined the ability of some phytochemicals, including alkaloids (glaucine, harmine, and sanguinarine), phenolics (EGCG and thymol), and terpenoids (menthol, aromadendrene, β-sitosterol-O-glucoside, and β-carotene), alone or in combination with the saponin digitonin to reverse the relative multi-drug resistance of Caco-2 and CEM/ADR5000 cells to the chemotherapeutical agent doxorubicin. The IC(50) of doxorubicin in Caco-2 and CEM/ADR5000 was 4.22 and 44.08μM, respectively. Combination of non-toxic concentrations of individual secondary metabolite with doxorubicin synergistically sensitized Caco-2 and CEM/ADR5000 cells, and significantly enhanced the cytotoxicity of doxorubicin. Furthermore, three-drug combinations (secondary metabolite+digitonin+doxorubicin) were even more powerful. The best synergist was the benzophenanthridine alkaloid sanguinarine. It reduced the IC(50) value of doxorubicin 17.58-fold in two-drug combinations (sanguinarine+doxorubicin) and even 35.17-fold in three-drug combinations (sanguinarine+digitonin+doxorubicin) in Caco-2 cells. Thus synergistic drug combinations offer the possibility to enhance doxorubicin efficacy in chemotherapy.
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