Verapamil enhances the uptake and the photocytotoxic effect of PII, but not that of tetra(4-sulfonatophenyl)porphine.
The influence of the calcium channel blocker verapamil on the sensitivity of mouse fibrosarcoma cells of the line EMT-6 to treatment with Photofrin II (PII) or tetra(4-sulfonatophenyl)porphine (TPPS4) and light has been assessed. Cells were treated with 1.5 microg/ml PII or 75 microg/ml TPPS4 overnight in the absence or presence of 50 microg/ml verapamil and subsequently exposed to light. Verapamil increased the sensitivity of the EMT-6 cells to PII-induced photoinactivation by a factor of 2. In contrast, verapamil decreased the sensitivity of the cells to TPPS4-induced photoinactivation by 50-60%. Both sensitizers were found to be located to a large extent in lysosomes as revealed by fluorescence microscopy and by photochemical inactivation of the lysosomal marker enzyme beta-N-acetyl-D-glucosaminidase. Verapamil increased the uptake of PII by 30% and reduced the uptake of TPPS4 by 20%. Furthermore, verapamil enhanced the binding and uptake of LDL by about 40%. In conclusion, the effects of verapamil-induced sensitization of EMT-6 cells treated with PII or TPPS4 and light can to a large extent be attributed to the modulatory effects of verapamil on endocytosis.
Berg
K
K
Institute for Cancer Research, Department of Biophysics, Montebello, N-0310 Oslo 3, Norway. kristian.berg@labmed.ui.no
Maziere
J C
JC
Geze
M
M
Santus
R
R
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D017323:Dihematoporphyrin Ether / Q000494:pharmacology*; D004357:Drug Synergism; D005354:Fibrosarcoma; D006801:Humans; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D008856:Microscopy, Fluorescence; D009499:Neutral Red; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*
D017319:Photosensitizing Agents; D011166:Porphyrins; D009499:Neutral Red; C016136:tetraphenylporphine sulfonate; D017323:Dihematoporphyrin Ether; D014700:Verapamil