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, 100μg/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.