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The effects of 9 calcium antagonists on ABCG2/BCRP-mediated resistance andtransport were examined in HeLa and SN-38-resistant HeLa (HeLa/SN100) cells, overexpressingABCG2/BCRP. Sensitivity to mitoxantrone, an ABCG2/BCRP substrate, in HeLa/SN100cells was significantly reversed by the coexistence of the calcium antagonists,except for diltiazem and verapamil. The accelerated transport activity of Hoechst33342,an ABCG2/BCRP substrate, in HeLa/SN100 cells was significantly decreased by thepresence of the calcium antagonists, except for diltiazem, nifedipine or verapamil,returning to the level of HeLa cells. The present study classifies the calciumantagonists into 3 categories: strong (benidipine, felodipine, nicardipine, nisoldipineand nitrendipine), moderate (amlodipine and nifedipine) and weak (diltiazem andverapamil) inhibitors of ABCG2/BCRP.

Differential effects of calcium antagonists on ABCG2/BCRP-mediated drug resistance and transport in SN-38-resistant HeLa cells