A novel polysaccharide from Se-enriched Ganoderma lucidum induces apoptosis of human breast cancer cells

Abstract

Abstract. The novel polysaccharide SeGLP-2B-1 isolated from Se-enriched Ganoderma lucidum, showed antiproliferative activity towards several cancer cell lines in vitro. To investigate the antitumor mechanisms, the apoptotic effects of SeGLP-2B-1 in human breast cancer cells were studied, and the mechanism of this action was further elucidated. Cell apoptosis was detected by Annexin V/PI staining. Caspase activity was assayed using a caspase apoptosis detection kit. Western blot analysis was used to evaluate the levels of procaspase-3, -8, -9, PARP and cytochrome c expression. The results showed that SeGLP-2B-1 inhibited the growth of MCF-7 cells in a time-and dose-dependent manner. Typical characteristics of apoptosis were observed, including morphological changes, sub-G1 cells and DNA ladder formation. Further analysis showed that SeGLP-2B-1 treatment disrupted the mitochondrial membrane potential followed by an increase in the cytochrome c cytosolic levels. Sequentially, SeGLP-2B-1 increased the activities of caspase-9, -3 and poly (ADPribose) polymerase in a time-dependent manner, however, no obvious activation of caspase-8 was observed. Caspase-9 and caspase-3 inhibitor prevented SeGLP-2B-1-induced apoptosis, and the activities of caspases-3, -9 were significantly upregulated by SeGLP-2B-1. Our studies suggest that SeGLP-2B-1 induces apoptosis via a mitochondria-mediated pathway. IntroductionEpidemiological studies suggest that dietary and chemoprevention can provide an important and potentially feasible pathway for reducing cancer occurrence. Selenium (Se) is an essential trace element for a number of metabolically important enzymes (1). Accumulating evidence indicates that a significant inverse relationship between intake of Se and cancer incidence and Se has received considerable attention for its potential role as a chemopreventive agent (2,3). Selenite induce cell necrosis accompanied by damage to cellular DNA and loss of cell-membrane integrity (4,5). Organic selenocompounds induced apoptosis (programmed cell death) without producing changes in membrane integrity or cellular DNA as measured by single-strand breaks in DNA (6-8). Both organic and inorganic compounds of Se have been demonstrated to manifest cancer preventive potential, but several organic seleno-compounds have shown higher anticancer activities, lower toxicity and fewer side effects than selenite, therefore, it is crucial to develop suitable organic Se sources for cancer chemoprevention.Se-containing polysaccharide, a nutritionally available organic seleno-compound, has been shown to promote cancer cell differentiation, suppress cell division and induce programmed cell death by regulating cancer gene expression (9,10). Although several mechanisms have been proposed to account for anticancer effects of Se-containing polysaccharide, selective induction of tumor cell apoptosis may be of particular significance as chemopreventive agents (11)(12)(13)(14).SeGLP-2B-1, a Se-containing polysaccharide, was purified and characterized from the Se-enr...

Comparison of multielemental composition of Polish and Chinese mushrooms (Ganoderma spp.)

“…As previously demonstrated, uptake of elements such as Se by G. lucidum can weaken the antitumor and immunomodulatory effects of its polysaccharides and proteins [34,35]. As demonstrated in the present study, the Se was detected only in some fruiting bodies with the highest mean contents identified for cultivated G. capense (1.37 mg kg −1 ) and G. lucidum (1.41 mg kg −1 ).…”

“…It should be highlighted that Al is poorly absorbed in the gastrointestinal tract (usually 0.1-1.0% of an oral dose) and in healthy subjects almost the entire amount of absorbed Al is excreted readily from the body [47]. Increased accumulation in humans, predominantly in the brain, occurs in patients suffering renal failure or if doses exceed excretory capacity [34], and has been implicated in neurodegenerative processes [48]. The provisional tolerable weekly intake (PTWI) for Al is 2 mg kg −1 body weight [49].…”

Co-nanoencapsulation of magnetic nanoparticles and selol for breast tumor treatment: in vitro evaluation of cytotoxicity and magnetohyperthermia efficacy

“…Apoptosis has been described as one of the more important mechanisms for the anticancer action of selenium-based compounds. [35][36][37] Although Valdiglesias et al 38 reported that the induction of apoptosis by Seleniumbased compounds may be related to changes in the cell cycle, Suchocki et al 20 found that free selol did not overset the cell cycle in human leukemia cells.…”

Ganoderma Lucidum Polysaccharides Target a Fas/Caspase Dependent Pathway to Induce Apoptosis in Human Colon Cancer Cells

“…Previous studies have showed that GLP can mediate cytotoxicity in number of cancer cell lines including lung cancer, prostate cancer and breast cancer. Further studies showed that GLP programmed cell death through endothelial growth factor overexpression and tumor angiogenesis inhibition in highly metastatic mouse melanoma B16F10 cells (Sun et al, 2011), through endotoxin-induced intercellular cell adhesion molecule-1 (ICAM-1) upregulation in the neointima in mice (Liu et al, 2010), through cell differentiation and p53 activation in human monocytic leukemia THP-1 cells (Hsu et al, 2011), through activation of mitochondrial signaling pathway in MCF-7 breast cancer cells (Shang et al, 2011). GLP can also boost anticancer immunity by changing lymphocyte phenotype in H22 hepatoma mice (Zhou et al, 2009), by enhancing CD56 + NK-cell cytotoxicity in cord blood (Chien et al, 2004), by promoting the proliferation of B cells in mice (Jiang et al, 2003).…”