Effects of benzopsoralen derivatives on HL60 and HeLa cells

Pharmacol Toxicol. 1996 Dec;79(6):340-6. doi: 10.1111/j.1600-0773.1996.tb00020.x.

Abstract

The effect of 4-hydroxymethyl-6,7,8,9-tetrahydro-2H-benzofuro-[3,2-g]-1-benzo piran-2-one (compound 1) and 4-hydroxymethyl-2H-benzofuro-[3,2g]-1-benzopiran-2-one (compound 2), two new benzopsoralen derivatives, was tested on HL60 and HeLa cell lines in the dark and by UVA irradiation; 8-methoxypsoralen was used as a reference compound. The action of the compounds was evaluated by means of the neutral red uptake assay, by means of ultrastructure, morphometry and interaction with human erythrocytes membrane. In both HL60 and HeLa cell lines benzopsoralen derivatives showed more antiproliferative activity after UVA irradiation, however less than 8-methoxypsoralen. Compound 1 was more effective than compound 2 both in the dark and after UVA irradiation. The ultrastructure showed a morphological rank damage caused by these compounds: compound 2 induced slight modifications in the cytoplasm organization, compound 1 induced some vacuolizations and 8-methoxypsoralen generated plenty of vacuoles and an empty space around the nucleus. Morphometrical data in HL60 cells turned out to be in accordance with the different action mechanisms existing between 8-methoxypsoralen and the two benzopsoralen derivatives; in HeLa cells we noted an increase in the nuclear area induced by all the three compounds. Only compound 1 caused the formation of echinocytes both in the dark and after UVA irradiation, suggesting the involvement of a mechanism not strictly related to DNA interaction and singlet oxygen production.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / drug effects
  • Cell Division / radiation effects
  • Dose-Response Relationship, Drug
  • Erythrocyte Membrane / drug effects*
  • Erythrocyte Membrane / radiation effects
  • Erythrocyte Membrane / ultrastructure
  • Furocoumarins / pharmacology*
  • HeLa Cells / drug effects
  • HeLa Cells / ultrastructure
  • Humans
  • Methoxsalen / pharmacology
  • Photosensitizing Agents / pharmacology*
  • Ultraviolet Rays

Substances

  • 4-hydroxymethyl-2H-benzofuro-(3,2-g)-1-benzopiran-2-one
  • 4-hydroxymethyl-6,7,8,9-tetrahydro-2H-benzofuro-(3,2-g)-1-benzopiran-2-one
  • Furocoumarins
  • Photosensitizing Agents
  • Methoxsalen