Intracellular distribution of anthracyclines in drug resistant cells

The unresponsiveness of multidrug resistant tumor cells to antineoplastic c hemotherapy is often associated with reduced cellular drug accumulation acc omplished by overexpressed transport molecules. Moreover, intracellular dru g distribution in resistant cells appears to be remarkably different when c ompared to their wild type counterparts. In the present paper, we report ob servations on the intracellular accumulation and distribution of doxorubici n, an antitumoral agent widely employed in chemotherapy, in sensitive and r esistant cultured tumor cells. The inherent fluorescence of doxorubicin all owed us to follow its fate in living cells by laser scanning confocal micro scopy. This study included flow cytometric analysis of drug uptake and effl ux and analysis of the presence of the well known drug transporter P-glycop rotein. Morphological, immunocytochemical and functional data evidentiated the Golgi apparatus as the preferential intracytoplasmic site of drug accum ulation in resistant cells, capable of sequestering doxorubicin away from t he nuclear target. Moreover, P-glycoprotein has been found located in the G olgi apparatus in drug induced resistant cells and in intrinsic resistant c ells, such as melanoma cells. Thus, this organelle seems to play a pivotal role in the intracellular distribution of doxorubicin.