INHIBITION OF THE ATPASE ACTIVITY OF P-GLYCOPROTEIN BY PORPHYRIN PHOTOSENSITIZATION OF MULTIDRUG-RESISTANT CELLS IN-VITRO

The effectiveness of photodynamic therapy against P-glycoprotein ATPase activity in multidrug-resistant cells was studied. Chinese hamster ovary AUXB1 (drag-sensitive) and CR1R12 (multidrug-resistant) cell lines were compared with respect to uptake of C-14-polyhematoporphyrin and porphyrin photosensitization. Phototoxicity of Photofrin(R) was similar in both cell lines, and no major differences in uptake or efflux of C-14-polyhematoporphyrin were observed. Porphyrin photosensitization in vitro of CR1R12 cells or isolated plasma membranes from these cells caused inhibition of P-glycoprotein ATPase activity. Application of porphyrin photosensitization at a sublethal level to CR1R12 cells resulted in a small but significant increase in adriamycin-induced cytotoxicity. The hydrophobic ''picket-fence'' porphyrin, meso-tetrakis-(o-propionamidophenyl)porphyrin,alpha,alpha,alpha,beta-isomer, was more inhibitory toward P-glycoprotein ATPase activity than the two less hydrophobic porphyrins tetraphenylporphine tetrasulfonate and Photofrin(R).