title: The Antioxidative Fraction of White Mulberry Induces Apoptosis through Regulation of p53 and NFκB in EAC Cells.
abstract: 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.
authors.affiliation: Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Ahm Khurshid
authors.initials: AK
authors.lastname: Alam
authors.affiliation: Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Asm Sakhawat
authors.initials: AS
authors.lastname: Hossain
authors.affiliation: Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh.
authors.forename: Muhammad Ali
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Syed Rashel
authors.initials: SR
authors.lastname: Kabir
authors.affiliation: Department of Genetic Engineering & Biotechnology, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Md Abu
authors.initials: MA
authors.lastname: Reza
authors.affiliation: Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Md Mahbubur
authors.initials: MM
authors.lastname: Rahman
authors.affiliation: Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Mohammad Saiful
authors.initials: MS
authors.lastname: Islam
authors.affiliation: Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Md Aziz Abdur
authors.initials: MA
authors.lastname: Rahman
authors.affiliation: Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Mamunur
authors.initials: M
authors.lastname: Rashid
authors.affiliation: Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Md Golam
authors.initials: MG
authors.lastname: Sadik
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D031625:Morus / Q000737:chemistry*; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics / Q000378:metabolism; D059808:Polyphenols / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000085:Acetates; D000975:Antioxidants; D016328:NF-kappa B; D059808:Polyphenols; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C007650:ethyl acetate; D000071137:Poly (ADP-Ribose) Polymerase-1