The Antioxidative Fraction Of White Mulberry Induces Apoptosis Through Regulation Of P53 And Nf Kappa B In Eac Cells

In this study, the antioxidative fraction of white mulberry (Morus alba) was found to have an apotogenic effect on Ehrlich's ascites carcinoma cell-induced mice (EAC mice) that correlate with upregulated p53 and downregulated NF kappa B signaling. The antioxidant activities and polyphenolic contents of various mulberry fractions were evaluated by spectrophotometry and the ethyl acetate fraction (EAF) was selected for further analysis. Strikingly, the EAF caused 70.20% tumor growth inhibition with S-phase cell cycle arrest, normalized blood parameters including red/white blood cell counts and suppressed the tumor weight of EAC mice compared with untreated controls. Fluorescence microscopy analysis of EAF-treated EAC cells revealed DNA fragmentation, cell shrinkage, and plasma membrane blebbing. These characteristic morphological features of apoptosis influenced us to further investigate pro-and anti-apoptotic signals in EAF-treated EAC mice. Interestingly, apoptosis correlated with the upregulation of p53 and its target genes PARP-1 and Bax, and also with the down-regulation of NF.B and its target genes Bcl-2 and Bcl-xL. Our results suggest that the tumor-suppressive effect of the antioxidative fraction of white mulberry is likely due to apoptosis mediated by p53 and NF kappa B signaling.