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.
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.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis*; D004910:Erythrocyte Membrane / Q000187:drug effects; D006367:HeLa Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006912:Hydroxyquinolines / Q000494:pharmacology*; D007399:Interphase / Q000187:drug effects; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015125:Oxyquinoline / Q000031:analogs & derivatives / Q000494:pharmacology*; D011817:Rabbits
D006912:Hydroxyquinolines; C010989:2-(2-hydroxy-5-n-hexylphenyl)-8-quinolinol-4-carboxylic acid; D015125:Oxyquinoline; D004247:DNA; D007501:Iron