Open AccessThe Antioxidative Fraction of White Mulberry Induces Apoptosis through Regulation of p53 and NFκB in EAC Cells
Author(s) -
Ahm Khurshid Alam,
Alamgir Hossain,
Muhammad Ali Khan,
Syed Rashel Kabir,
Abu Reza,
Mahbubur Rahman,
Mohammad Saiful Islam,
Aziz Abdur Rahman,
Mamunur Rashid,
Golam Sadik
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0167536
Subject(s) - apoptosis , downregulation and upregulation , dna fragmentation , chemistry , fragmentation (computing) , signal transduction , microbiology and biotechnology , biology , programmed cell death , biochemistry , gene , ecology
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 NFκB 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 NFκB 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 NFκB signaling.