Taxonomic group: fungi / Ascomycota
(Phylum: Ascomycota)
NCBI PubMed ID: 26255117Publication DOI: 10.1016/j.biocel.2015.08.003Journal NLM ID: 9508482Publisher: Amsterdam: Elsevier
Correspondence: Dekker RF <rdekker
lakeheadu.ca>; Dekker RF <xylanase
gmail.com>; Khaper N <nkhaper
nosm.ca>
Institutions: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil, Departamento de Química, Universidade Tecnológica Federal do Paraná, Pato Branco, Brazil, Biorefining and Biotechnology Consultancy, Londrina, Brazil, Biorefining Research Institute (BRI), Lakehead University, Thunder Bay, Canada, Medical Sciences Division, Northern Ontario School of Medicine (NOSM), Lakehead University, Thunder Bay, Canada
Fungal β-D-glucans of the (1→3)-type are known to exhibit direct antitumor effects, and can also indirectly decrease tumor proliferation through immunomodulatory responses. The underlying molecular mechanisms involved in decreasing tumor formation, however, are not well understood. In this study, we examined the antiproliferative role and mechanism of action of three different fungal exocellular β-glucans in MCF-7 breast cancer cells. The β-glucans were obtained from Botryosphaeria rhodina MAMB-05 [two botryosphaerans; (1→3)(1→6)-β-D-glucan; one produced on glucose, the other on fructose] and Lasiodiplodia theobromae MMPI [lasiodiplodan; (1→6)-β-D-glucan, produced on glucose]. Using the cell proliferation-MTT assay, we showed that the β-glucans exhibited a time- and concentration-dependent antiproliferative activity (IC50, 100 μg/ml). Markers of cell cycle, apoptosis, necrosis and oxidative stress were analyzed using flow cytometry, RT-PCR and Western blotting. Exposure to β-glucans increased apoptosis, necrosis, oxidative stress, mRNA expression of p53, p27 and Bax; the activity of AMP-activated protein-kinase, Forkhead transcription factor FOXO3a, Bax and caspase-3; and decreased the activity of p70S6K in MCF-7 cells. In the presence of hydrogen peroxide, the fungal β-glucans increased oxidative stress, which was associated with reduced cell viability. We showed that these β-glucans exhibited an antiproliferative effect that was associated with apoptosis, necrosis and oxidative stress. This study demonstrated for the first time that the apoptosis induced by β-glucans was mediated by AMP-activated protein-kinase and Forkhead transcription factor, FOXO3a. Our findings provide novel mechanistic insights into their antiproliferative roles, and compelling evidence that these β-glucans possess a broad range of biomodulatory properties that may prove useful in cancer treatment
apoptosis, oxidative stress, Botryosphaeran, lasiodiplodan, AMPK, FOXO3a
Structure type: homopolymer
Location inside paper: abstract
Trivial name: pustulan, β-1,6-glucan, β-1,6-D-glucan, β(1-6)-D-glucan, β-(1,6)-glucan, lasiodiplodan, pustulan, β-(1,6)-glucan, lasiodiplodan, β-(1,6)-glucan, β-(1,6)-glucan, lasiodiplodan, pustulan, β-1,6-glucan, β-(1,6)-glucan, pustulan, β-(1→6)-glucan PCPS, water-soluble glucan (PS-I)
Compound class: EPS, O-polysaccharide, cell wall polysaccharide, glycoprotein, glucan, polysaccharide, cell wall glucoprotein
Contained glycoepitopes: IEDB_135614,IEDB_141806,IEDB_142488,IEDB_146664,IEDB_241101,IEDB_983931,SB_192
Methods: Western blotting, biological assays, RT-PCR, cell growth, dialysis, enzymatic assay, flow cytometry analysis, cell viability assay, precipitation, centrifugation, MTT
Biological activity: polysaccharide significantly increases mRNA expression of p53 (TP53 gene) after 48 h of treatment. Polysaccharide increases phosphorylation of AMPK, p-p70S6K (Thr389) expression in MCF-7 cells, the protein expression of Bax and the Bax/Bcl-2 ratio indicating the involvement of this pathway in apoptosis. Polysaccharide increases caspase-3 expression and also increases protein expression of Bcl-2 in MCF-7 cells
Related record ID(s): 7724, 8325, 42140, 43301, 43379, 44888, 44927, 44939, 45578, 47842, 47843, 48303, 48366, 48412, 48423, 48442, 49291, 101372, 124916, 138263, 143680, 143682, 149870
NCBI Taxonomy refs (TaxIDs): 45133Reference(s) to other database(s): GTC:G26777BZ, GlycomeDB:
863, CCSD:
50854, CBank-STR:4234
Show glycosyltransferases
There is only one chemically distinct structure:
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