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 M CF-7 and multidrug-resistant MCF-7/Dox human breast carcinoma cells. I n clonogenic assays, MCF-7/Dox cell was about 135fold less sensitive t o doxorubicin than MCF-7 cells. Caffeic acid (10 mu M) slightly altere d the colony forming ability of MCF-7 cells, and markedly reduced the IC50 of doxorubicin (Dox) from 10.8+/-1.3 mu M to 0.83+/-0.21 mu M in MCF-7/Dox cells. When compared to MCF-7/Dox cells, intracellular accum ulations of [C-14]Dox in MCF-7 cells for 1 hour and 12 hours were elev ated 2.3-fold and about 6.4-fold respectively. Doxorubicin accumulatio ns in MCF-7 and MCF-7/Dox cells were not altered in the presence of 10 mu M caffeic acid. Both TGF beta 1 and TGF beta 2 isotypes were detec ted 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 mu M), 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 ca ffeic acid is potentially a chemosensitizing agent with greater select ivity to drug-resistant MCF-7/Dox cells over parent MCF-7 cells and th at the chemosensitizing effect is not mediated by altered drug concent rations in the cells, but may be possibly correlated to the induction of TGF beta isotypes.