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INHIBITION OF THE ATPase ACTIVITY OF P‐GLYCOPROTEIN BY PORPHYRIN PHOTOSENSITIZATION OF MULTIDRUG‐RESISTANT CELLS in vitro
Author(s) -
Gibson Scott L.,
AlShawi Marwan K.,
Senior Alan E.,
Hilf Russell
Publication year - 1995
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1995.tb08628.x
Subject(s) - porphyrin , phototoxicity , p glycoprotein , chinese hamster ovary cell , in vitro , photodynamic therapy , chemistry , efflux , cytotoxicity , atpase , multiple drug resistance , hamster , cell culture , glycoprotein , biochemistry , microbiology and biotechnology , biology , enzyme , receptor , genetics , organic chemistry , antibiotics
— 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 14 C‐polyhematoporphyrin and porphyrin photosensitization. Phototoxicity of Photofrin® was similar in both cell lines, and no major differences in uptake or efflux of 14 C‐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,α,α,α,β‐isomer, was more inhibitory toward P‐glycoprotein ATPase activity than the two less hydrophobic porphyrins tetraphenylporphine tetrasulfonate and Photofrin®.