Chemosensitizing activity of caffeic acid in multidrug-resistant MCF-7/Dox human breast carcinoma cells

The chemosensitizing activity of caffeic acid was examined in parent MCF-7 and multidrug-resistant MCF-7/Dox human breast carcinoma cells. In clonogenic assays, MCF-7/Dox cell was about 135-fold less sensitive to doxorubicin than MCF-7 cells. Caffeic acid (10 microM) slightly altered the colony-forming ability of MCF-7 cells, and markedly reduced the IC50 of doxorubicin (Dox) from 10.8 +/- 1.3 microM to 0.83 +/- 0.21 microM in MCF-7/Dox cells. When compared to MCF-7/Dox cells, intracellular accumulations of [14C] Dox in MCF-7 cells for 1 hour and 12 hours were elevated 2.3-fold and about 6.4-fold, respectively. Doxorubicin accumulations in MCF-7 and MCF-7/Dox cells were not altered in the presence of 10 microM caffeic acid. Both TGF beta 1 and TGF beta 2 isotypes were detected in MCF-7/Dox cells, while only TGF beta 1 was found in MCF-7 cells. The level of TGF beta 1 in MCF-7/Dox cells was about 3-fold greater than that in MCF-7 cells. In cells pretreated with caffeic acid (10 microM), TGF beta 1 and TGF beta 2 levels were overexpressed only in MCF-7/Dox cells by 90% and 60%, respectively. These results suggest that caffeic acid is potentially a chemosensitizing agent with greater selectivity to drug-resistant MCF-7/Dox cells over parent MCF-7 cells and that the chemosensitizing effect is not mediated by altered drug concentrations in the cells, but may be possibly correlated to the induction of TGF beta isotypes.