Clofazimine and B4121 sensitize an intrinsically resistant human colon cancer cell line to P-glycoprotein substrates

The potential of B4121 to sensitize three intrinsically resistant human col on cancer cell lines (CaCo2, ATCC HTB 37; COLO 32 DM, ATCC CCL 220; HT-29, ATCC HTB 38) to vinblastine, doxorubicin, daunorubicin, paclitaxel, taxoter e and cisplatin at a non-toxic, therapeutically relevant concentration of 0 .25 mu g/ml was compared with that of clofazimine at a similar concentratio n. The cell line expressing high levels of P-glycoprotein (P-gp), COLO 320 DM, was susceptible to chemosensitization by the experimental agents for th e P-gp substrates (paclitaxel, taxotere, daunorubicin, vinblastine and doxo rubicin) but not for cisplatin. CaCo2 cells expressed lower levels of P-gp and were only marginally susceptible to sensitization by any one of these d rugs, except in the case of sensitization by B4121 for doxorubicin and taxo tere, whereas the HT-29, a P-gp negative cell line, was unaffected. The rim inophenazines, especially B4121, might prove useful as combination treatmen t in circumventing P-gp mediated resistance of colon cancers.