Cell growth inhibition and cell cycle perturbations induced by a new synthetic iminoquinone, 5H-pyridophenoxazin-5-one, in human breast carcinoma cell lines

摘要

5H-Pyridophenoxazin-5-one (PPH) is a new synthetic iminoquinone which has showed to be a potent cytotoxic agent on different cancer cell lines. PPH effects depend by the intercalation into the DNA double strand at the middle 50-GC-30 base pairs of the octamer [d(GAAGCTTC)2] and the production, under bio reductive conditions, of free oxygen radicals. The aim of the study was to analyse cell growth and cell cycle kinetics of MCF-7 (p53 wt) and MDAMB- 468 (p53 mut) human breast cancer cell lines after PPH exposure. Treatments were performed with different PPH concentrations (ranging from 0.5 mM up 8 mM) as pulsed (60 min/exposure) or continuous exposure. MCF-7 cells were more sensitive to pulsed treatment than MDA-MB-468 cell line. Cell cycle analysis by PI staining showed a G2M perturbation that was overcome after 72 hours in both cell lines. As expected, continuous treatment caused a strongest cell-growth inhibition and cell cycle perturbation in both cell lines. However, DNA-flow cytometry showed that MCF-7 cells cytotoxicity correlate with an accumulation of cells in the S phase, whereas an irreversible G2M block accompanied MDA-MB-468 cytotoxicity.