Anticancer properties of low molecular weight oat beta-glucan – An in vitro study
Abstract
Anticancer properties of 1–3, 1–4 oat beta glucan are under intensive investigation now. Antitumor characteristic of fungi and yeast beta-glucans have been widely recognized, but those polysaccharides are mostly insoluble which creates several problems especially in topical formulation. Also high molecular weight oat beta-glucans reveal high viscosity which restricts its application. According to those problems in the current study the antitumor activities of low molecular weight beta-glucan derived from oats were investigated in cancer cells: Me45, A431 and normal HaCaT and murine macrophages P388/D1. The low molecular weight beta-glucan from oat significantly deceased cancer cells viability, while for the normal cells it was non-toxic. It was observed that with the increasing incubation time and the beta-glucan concentration the cancer cells viability significantly deceased. Furthermore for the normal cells the low molecular weight beta-glucan from oat was non-toxic. Immunocytochemical ABC analysis showed that beta-glucan induced strong expression of caspase-12 in both cancer cell lines, while in HaCaT cells ABC reaction was significantly lower and in P388/D1 cell line ABC reaction was negative. Our preliminary studies show strong anti-tumor properties of new low molecular weight beta-glucan from oat and at the same time no toxicity for normal cells.
Introduction
The cancer as a broad group of diseases involving unregulated cell growth is diverse, complex, and only partially understood, what makes it difficult to cure [1]. Melanoma is the most serious type of skin cancer because of its ability to grow rapidly and to metastasize. There is no fully effective treatment and scientists are still seeking an effective way to combat this cancer [2]. Non-prescriptional usage of medicinal herbs among cancer patients including skin cancer patients is more often common and relates to standard treatment methods results, accessibility to standard treatments and medical treatment heritage [3].
The current information suggests that herbal extracts exert biological effect through cytotoxic or immunomodulatory mechanisms. In cancer therapy many cytotoxic chemotherapeutic agents are applied such as taxol, etoposide or vincristine [4]. However there is a need for new and natural anticancer compounds of low or without toxicity to normal cells. One of the active compounds responsible for the immune effects is β-glucan sourced from cereals, fungi, seaweeds, yeasts and bacteria [3], [5], [6], [7], [8], [9], [10]. Current data suggests that β-glucans are very potent immunomodulators with effects on innate and adaptive immunity [3]. Based on in vitro studies, β-glucans act on several immune receptors, e.g. dectin-1 and trigger a group of immune cells including monocytes, macrophages, neutrophils, natural killer cells and dendritic cells [3], [11], [12], [13], [14]. The entire signaling pathway downstream to dectin-1 activation leads to the release of cytokines including interleukin IL-12, IL-6, tumor necrosis factor (TNF), and IL-10. Some of these cytokines may play important role in the cancer therapy [3]. Other important β-glucan receptors mediating anti-tumor and anti-infective properties are receptor 3 (CR3; CD11b/CD18) [15], [16] and lactosylceramide [17]. The antitumor effect of glucan can be attributed to cancer-preventing, immune-enhancing and direct tumor inhibition activities [18].
In vivo studies showed that after oral administration the specific backbone 1,3 linear β-glycosidic chain of β-glucans cannot be digested. β-glucans enter the proximal small intestine; some are captured by the macrophages, internalized and fragmented within the cells [19]. After fragmentation beta-glucans are transported by the macrophages to the marrow and endothelial reticular system. These small fragments are released by the macrophages and taken up by other immune cells. This leads to various immune responses. Nevertheless, depending on the different sizes and branching patterns, β-glucans may have significantly variable immune potential [2], [18], [19], [20], [21], [22], [23], [24].
Beta-glucan concentrates isolated from cell wall of yeast or fungi not only has low yield but inflammation, granuloma formation and microembolization after intravenous administration are occurring as well [8], [9], [18], [21], [25], [26]. In terms of extracellular beta-glucan produced by microorganisms, the industrial use of lyophilized beta-glucan is limited due to the high cost of manufacturing dehydrated products and induction of bacteria [7], [8]. 1–3, 1–4 oat glucan is a compound of good solubility in water and reveals strong biological activity. Oat (1 → 3), (1 → 4)-β-d-glucans (oat β-glucan) are part of the human diet and they can contact with enterocytes, M-cells, and DCs, which are all present at the intestinal immune system and can enhance its function [27], [28]. For this reason, the 1–3, 1–4 beta glucan sourced from oat is the focus of this study. Importantly, it is water soluble, which greatly facilitates its practical application. As the matter of fact the question how the physicochemical characteristics affects the function is still open and no real conclusion was ever reached. The problem needs to be further investigated to achieve critical mass of data enabling proper concluding.
The aim of the study was to evaluate the antitumor activities of low molecular weight (LMW) beta-glucan derived from oat, on the human epidermoid carcinoma and human malignant melanoma cells.
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