DNA-Binding, Photocleavage, and Photodynamic Anti-cancer Activities of Pyridyl Corroles

J Membr Biol. 2016 Aug;249(4):419-28. doi: 10.1007/s00232-016-9879-0. Epub 2016 Feb 19.

Abstract

The DNA-binding, photocleavage, and antitumor activity of three free base pyridyl corroles 1, 2, and 3 have been investigated. The binding affinity toward CT-DNA decreases with increasing number of pentafluorophenyl, whereas the photocleavage activity toward pBR322 DNA becomes more efficient. Singlet oxygen was demonstrated as active species responsible for DNA cleavage. These corroles exhibited high cytotoxicity against three tested cancer cells (Hela, HapG2, and A549) and the cytotoxicity could be further enhanced under irradiation. Intracellular reactive oxygen species level was also monitored using HeLa Cells upon the combined treatment of corroles and light. These corroles could be absorbed by HeLa cells at low concentration. They can induce the decrease of mitochondrial membrane potential and apoptosis of tumor cells under irradiation.

Keywords: Apoptosis; Corrole; DNA; Photocytotoxicity; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA / chemistry
  • DNA / metabolism*
  • DNA Cleavage / drug effects*
  • DNA Cleavage / radiation effects*
  • Humans
  • Inhibitory Concentration 50
  • Light*
  • Membrane Potential, Mitochondrial / drug effects
  • Molecular Structure
  • Porphyrins / chemistry
  • Porphyrins / pharmacology*
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Porphyrins
  • Reactive Oxygen Species
  • corrole
  • DNA