P-glycoprotein (Pgp) does not affect the cytotoxicity of flavonoids from Sophora flavescens, which also have no effects on Pgp action
Choi, S.U.; Kim, K.H.; Choi, E.J.; Park, S.H.; Lee, C.O.; Jung, N.P.; Yoon, S.K.; Ryu, S.Y.
Anticancer Research 19(3a): 2035-2040
1999
ISSN/ISBN: 0250-7005 PMID: 10470145 Document Number: 507834
Sophoraflavanone, kurarinone (GS08), norkurarinol (GS11), kurarinol (GS12) and kushenol K are cytotoxic flavonoids isolated from S. flavescens. In this study, the cytotoxicity of these flavonoids to human cancer cells including P-glycoprotein (Pgp)-expressing HCT15 cells and its multidrug resistant subline, HCT15/CL02 cells was studied. 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 the flavonoids tested. At nontoxic concentrations, the flavonoids did not affect 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 micro M. From the results, it is concluded that Pgp had no effect on the cytotoxicity of the flavonoids, and the flavonoids also had no effect on the action of Pgp. The results also suggest that HCT15/CL02 cells have additional mechanisms for drug resistance distinct from Pgp overexpression.