Enhancement of Nile blue derivative-induced photocytotoxicity by nigericin and low cytoplasmic pH.
The mechanism of photocytotoxicity mediated by a lysosomotropic photosensitizer, Nile blue derivative (NBS-61), in relation to lysosome destruction was examined by lowering the intracellular pH with low extracellular pH and an ionophore, nigericin. The treatment performed after photoirradiation had minimal effect on the cytotoxicity. However, when the treatment was initiated before photoirradiation, it caused a three orders of magnitude enhancement on cytotoxicity with a two orders of magnitude enhancement by nigericin alone. This effect on cytotoxicity resembles closely that observed on photosensitization mediated by chloroaluminum phthalocyanine. The enhancement in this case has been attributed to the synergistic interaction between photodamage and perturbation of ion transports across mitochondrial or plasma membranes by nigericin. Because these are not the main sites of localization for Nile blue photosensitizers nor their initial targets of photocytotoxic action, data from the present study suggest the possibility of an intracellular dye translocation induced by nigericin, which redistributes the Nile blue photosensitizer from lysosomes to other sites, as a possible cause of the enhancement of cytotoxicity.
Lin
C W
CW
Urology Research Laboratory, Massachusetts General Hospital, Boston.
Shulok
J R
JR
D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000187:drug effects / Q000528:radiation effects; D009550:Nigericin / Q000494:pharmacology*; D010078:Oxazines / Q000737:chemistry / Q000494:pharmacology*; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects
D010078:Oxazines; D017319:Photosensitizing Agents; C008619:Nile Blue; D009550:Nigericin