Verapamil enhances the uptake and the photocytotoxic effect of PII, but not that of tetra(4-sulfonatophenyl)porphine

Biochim Biophys Acta. 1998 Mar 13;1370(2):317-24. doi: 10.1016/s0005-2736(97)00282-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Dihematoporphyrin Ether / pharmacology*
  • Drug Synergism
  • Fibrosarcoma
  • Humans
  • Mammary Neoplasms, Experimental
  • Mice
  • Microscopy, Fluorescence
  • Neutral Red
  • Photosensitizing Agents / pharmacology*
  • Porphyrins / pharmacology*
  • Tumor Cells, Cultured
  • Verapamil / pharmacology*


  • Photosensitizing Agents
  • Porphyrins
  • Neutral Red
  • tetraphenylporphine sulfonate
  • Dihematoporphyrin Ether
  • Verapamil