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 5′-GC-3′ 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 MDA-MB-468 (p53 mut) human breast cancer cell lines after PPH exposure. Treatments were performed with different PPH concentrations (ranging from 0.5 μM up 8 μM) 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.

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

F. Sabbatino;PEPE, Stefano
2007-01-01

Abstract

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 5′-GC-3′ 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 MDA-MB-468 (p53 mut) human breast cancer cell lines after PPH exposure. Treatments were performed with different PPH concentrations (ranging from 0.5 μM up 8 μM) 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.
2007
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11386/3881460
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact