P-gp modulating effect of Azadirachta indica extract in multidrug-resistant cancer cell lines

The extract of Azadirachta indica, commonly known as neem, has found extensive use in traditional medicine for treating various human diseases. In this study, the effect of the 50% ethanol extract of A. indica (A101) on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) was examined using MDR cell lines, specifically paclitaxel-resistant HepG2 (PR-HepG2) and doxorubicin (DOX)-resistant (DR) colon-26 cells. 96-h treatment of the two cell lines with A101 (30 mu g/mL) showed no effect on the expression of P-gp mRNA (human MDR1 and mouse mdr1b) and protein, while A101 increased the accumulation of rhodamine 123, a P-gp substrate, in both PR-HepG2 and DR-colon-26 cells. The cytotoxic effects of 48-h treatment with A101 on the viability of PR-HepG2 and DR-colon-26 cells were not observed. Therefore, 30 mu g/mL A101 may have no cytotoxic and P-gp-inducing effects. Finally, A101 potentiated the sensitivity of PR-HepG2 and DR-colon-26 cell lines to DOX by 8.6- and 15.3-fold, respectively. These findings suggest that A. indica may be a promising source for a new class of P-gp modulators without cytotoxic/P-gp induction effects.