Effect of an antitumor chelator, 2-(2-hydroxy-5-n-hexylphenyl)-8-quinolinol-4-carboxylic acid (HQ-II) on DNA synthesis, clonogenicity, and cell cycle progression of HeLa cells

Abstract

A newly synthesized antitumor chelator, 2-(2-hydroxy-5-n-hexylphenyl)-8-quinolinol-4-carboxylic acid (HQ-II), was further investigated for the mechanism of action, employing a HeLa cell line. As the result, HQ-II prevented proliferation of HeLa cells in culture and the inhibition was ascribable to the interference of HQ-II with extra and/or intracellular iron component vital for cell growth. HQ-II selectively inhibited DNA biosynthesis and the inhibition resumed by washing out of the agent or by adding ferric or ferrous salts. The cell cycle progression was blocked at G1/S boundary phase by an exposure of 0.07 mM HQ-II. Cells washed out of the agent could synchronously traverse through S phase to mitosis with an index of synchrony of 0.48. However, HQ-II at much higher concentrations resulted in prolongation of S, G2, and G1 phases, in keeping with the result of cell kill kinetic analysis, which indicated that HQ-II was a S phase-specific but self-limiting agent. A ratio of B/A, where A is the concentration causing 50% inhibition of HeLa cell growth and B is that of the DNA biosynthesis, was found to be an effective criterion for screening antitumor agent among metal binding agents, chelators.