In vitro induction of apoptosis and in vivo effects of a flavone nitroderivative in murine mammary adenocarcinoma cells

✍ Scribed by Mariano G. Cárdenas; Elsa Zotta; Mariel Marder; Leonor P. Roguin

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: French
• Weight: 460 KB
• Volume: 125
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.24361

✦ Synopsis

Abstract

We explored the in vitro and in vivo mechanism of antitumor action of the synthetic flavonoid 2′‐nitroflavone on LM3 murine mammary adenocarcinoma cells. In vitro assays showed that 2′‐nitroflavone increased the population of LM3 hypodiploid cells and produced a typical ladder of DNA fragmentation. Apoptotic cell death was also characterized by the activation of caspase‐8, ‐9 and ‐3, by an increment in the expression levels of the proapoptotic protein Bax and by the release of cytochrome c to cytosol. The in vivo effect of 2′‐nitroflavone on tumor growth was studied in BALB/c mice injected subcutaneously with LM3 cells. Results showed that tumor volume and weight were significantly reduced at doses of 10 and 40 mg/kg of 2′‐nitroflavone, respectively. Apoptotic cells were identified by TUNEL assay in tumor slices from mice treated with 10 mg/kg of 2′‐nitroflavone. Western blot analysis of tumor lysate supernatants from treated mice revealed an upregulation of the total levels of Bax and Fas receptor. In addition, administration of 40 mg/kg of 2′‐nitroflavone to nontumor‐bearing mice showed no histopathological effects on different organ tissues. This is the first report of the in vivo growth inhibitory effect of 2′‐nitroflavone as an apoptotic agent likely useful for mammary adenocarcinoma treatment. © 2009 UICC