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 (drug-sensitive) and CR1R12 (multidrug-resistant) cell lines were compared with respect to uptake of 14C-polyhematoporphyrin and porphyrin photosensitization. Phototoxicity of Photofrin was similar in both cell lines, and no major differences in uptake or efflux of 14C-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.
Gibson
S L
SL
Department of Biochemistry, University of Rochester, School of Medicine and Dentistry, NY 14642, USA.
al-Shawi
M K
MK
Senior
A E
AE
Hile
R
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000528:radiation effects; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D018432:Drug Resistance, Multiple; D017324:Hematoporphyrin Derivative / Q000494:pharmacology; D006801:Humans; D010777:Photochemistry; D010778:Photochemotherapy; D011166:Porphyrins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011166:Porphyrins; D017324:Hematoporphyrin Derivative; D000251:Adenosine Triphosphatases