Differential antiproliferative and apoptotic response of sanguinarine for cancer cells versus normal cells

Sanguinarine, derived from the root of Sanguinaria canadendid, has been sho wn to possess antimicrobial, antiinflammatory, and antioxidant properties. Here we compared the antiproliferative and apoptotic potential of sanguinar ine against human epidermoid carcinoma (A431) cells and normal human epider mal keratinocytes (NHEKs), Sanguinarine treatment was found to result in a dose-dependent decrease in the viability of A431 cells as well as NHEKs alb eit at different levels because sanguinarine-mediated loss of viability occ urred at lower doses and was much more pronounced in the A431 carcinoma cel ls than in the normal keratinocytes. DNA ladder assay demonstrated that com pared to vehicle-treated control, sanguinarine treatment of A431 cells resu lted in an induction of apoptosis at 1-, 2-, and 5-mu M doses, Sanguinarine treatment did not result in the formation of a DNA ladder in NHEKs, even a t the very high dose of 10 mu M. The induction of apoptosis by sanguinarine was also evident by confocal microscopy after labeling the cells with anne xin V. This method also identified necrotic cells, and sanguinarine treatme nt also resulted in the necrosis of A431 cells. The NHEKs showed exclusivel y necrotic staining at high doses (2 and 5 mu M). We also explored the poss ibility of cell cycle perturbation by sanguinarine in A431 cells, The DNA c ell cycle analysis revealed that sanguinarine treatment did not significant ly affect the distribution of cells among the different phases of the cell cycle in A431 cells. We suggest that sanguinarine could be developed as an anticancer drug.