P-glycoprotein (Pgp) does not affect the cytotoxicity of flavonoids from Sophora flavescens, which also have no effects on Pgp action.

Sophoraflavanone, kurarinone (GS08), norkurarinol (GS11), kurarinol (GS12) and kushenol K are cytotoxic flavonoids isolated from Sophora flavescens. In this study, we tested the cytotoxicity of those flavonoids to human cancer cells including P-glycoprotein (Pgp)-expressing HCT15 cells and its multidrug resistant subline, HCT15/CL02 cells. HCT15/CL02 cells revealed resistance to GS08, GS11 and GS12 about 2 fold in comparison with HCT15 cells. Nonetheless, verapamil, a Pgp inhibitor, could not increase the cytotoxicity of all the flavonoids tested. We also investigated that the flavonoids could modulate the Pgp action. At nontoxic concentrations, theflavonoids could not effect on the cytotoxicity of paclitaxel, a well-known Pgp-substrate. The flavonoids also had no effects on the accumulation of rhodamine 123 in all the cells tested at 10 μM. From the results, we concluded that Pgp had no effect on the cytotoxicity of the flavonoids, and the flavonoids also had no effect on the action of Pgp. Our results also suggested that HCTI5/CL02 cells had additional mechanisms for drug resistance distinct from Pgp overexpression.