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

CÁRDENAS MARIANO; ZOTTA E; MARDER, M; ROGUIN, L. P

INTERNATIONAL JOURNAL OF CANCER. JOURNAL INTERNATIONAL DU CANCER.

Wiley InterScience.

Lugar: Hoboken, NJ, USA; Año: 2009 vol. 125 p. 222 - 228

0020-7136

We explored the mechanism of antitumor action in vitro of the synthetic flavonoid 2´-nitroflavone on LM3 murine mammary adenocarcinoma cells and then examined the in vivo effect of this derivative on the growth of LM3 cells injected in BALB/c mice. In vitro assays showed that 2´-nitroflavone increased the population of LM3 hypodiploid cells and produced a typical ladder of DNA fragmentation, suggesting the induction of apoptosis. Apoptotic cell death was characterized by the activation of caspase-8, -9 and -3, by an increment in the expression levels of the pro-apoptotic 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. Seven days after cell inoculation, 2´-nitroflavone was administrated i.p. twice a week for 3 weeks at doses of 1, 10 or 40 mg/kg/mouse. The control group received only 0.2 ml of vehicle. Results showed that tumor volume was reduced 70% and 43% (p