The influence of the cysteine protease inhibitor L-trans-epoxysuccinyl-leucyl amido(4-guanidio)butane (E64) on photobiological effects of tetra(4-sulfonatophenyl)porphine.
Human cervix carcinoma cells of the line NHIK 3025 were exposed to light after 18 h incubation with tetra(4-sulfonatophenyl)porphine (TPPS4) in the absence or presence of the cysteine protease inhibitor L-trans-epoxysuccinyl-leucyl amido(4-guanidino)butane (E64) followed by 1 h in sensitizer-free medium. E64 changed the photochemical properties of TPPS4 in NHIK 3025 cells, i.e., TPPS4 fluorescence yield was enhanced 2.5-fold and photochemically induced lysosomal rupture and loss of cell bound TPPS4 were inhibited. Additionally, E64 slightly (10%) reduced the sensitivity of the NHIK 3025 cells to photoinactivation. This is not likely to be due to its inhibitory effect on protease activity, but correlates with its inhibition of lysosomal rupture. The present results indicate that the release of lysosomal cysteine proteases from the lysosomal compartments are of little or no importance in the photochemical inactivation of NHIK 3025 cells when TPPS4 is used as photosensitizer.
Berg
K
K
Institute for Cancer Research, Department of Biophysics, Montebello, Oslo, Norway.
Moan
J
J
D002278:Carcinoma in Situ / Q000188:drug therapy; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism; D003131:Combined Modality Therapy; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010778:Photochemotherapy; D011166:Porphyrins / Q000493:pharmacokinetics / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
D015853:Cysteine Proteinase Inhibitors; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C016136:tetraphenylporphine sulfonate; D002403:Cathepsins; D007930:Leucine; C024974:E 64