Mushroom Ganoderma lucidum Prevents Colitis-Associated Carcinogenesis in Mice

Abstract

BackgroundEpidemiological studies suggest that mushroom intake is inversely correlated with gastric, gastrointestinal and breast cancers. We have recently demonstrated anticancer and anti-inflammatory activity of triterpene extract isolated from mushroom Ganoderma lucidum (GLT). The aim of the present study was to evaluate whether GLT prevents colitis-associated carcinogenesis in mice.Methods/Principal FindingsColon carcinogenesis was induced by the food-borne carcinogen (2-Amino-1-methyl-6-phenylimidazol[4,5-b]pyridine [PhIP]) and inflammation (dextran sodium sulfate [DSS]) in mice. Mice were treated with 0, 100, 300 and 500 mg GLT/kg of body weight 3 times per week for 4 months. Cell proliferation, expression of cyclin D1 and COX-2 and macrophage infiltration was assessed by immunohistochemistry. The effect of GLT on XRE/AhR, PXR and rPXR was evaluated by the reporter gene assays. Expression of metabolizing enzymes CYP1A2, CYP3A1 and CYP3A4 in colon tissue was determined by immunohistochemistry. GLT treatment significantly suppressed focal hyperplasia, aberrant crypt foci (ACF) formation and tumor formation in mice exposed to PhIP/DSS. The anti-proliferative effects of GLT were further confirmed by the decreased staining with Ki-67 in colon tissues. PhIP/DSS-induced colon inflammation was demonstrated by the significant shortening of the large intestine and macrophage infiltrations, whereas GLT treatment prevented the shortening of colon lengths, and reduced infiltration of macrophages in colon tissue. GLT treatment also significantly down-regulated PhIP/DSS-dependent expression of cyclin D1, COX-2, CYP1A2 and CYP3A4 in colon tissue.ConclusionsOur data suggest that GLT could be considered as an alternative dietary approach for the prevention of colitis-associated cancer.

Yeast-Derived ? -Glucan Reduces Intestinal Injury in Rat Model of Necrotizing Enterocolitis

“…New studies have shown that glucan exhibits prebiotic properties supporting the growth of probiotic bacteria [23]. However, only a few recently published studies evaluated the effects of glucan on the gastrointestinal tract [6][7] and none of them used glucan in the model of developing GI tract. In the present study, for the first time, we report that supplementation of glucan into milk formula reduces the incidence and severity of NEC in a neonatal rat model of NEC.…”

“…However, only a few recently published studies have tested the effect of glucans on the gastrointestinal (GI) tract [4,5], with particular interest in colitis [6][7][8]. As the effects of glucans on the development of neonatal intestinal injury have not been studied yet, this study describes new effects of glucan.…”

From 2000years of Ganoderma lucidum to recent developments in nutraceuticals

“…These include direct inhibition of cell proliferation through cancer-specific cell cycle arrest and apoptosis (Fukuzawa et al, 2008;Jedinak et al, 2011;Tang et al, 2006;Wu et al, 2012). In addition, a number of researchers have shown that treatment of cancer cells with G. lucidum extracts can lead to down-regulation of cell cycle-associated proteins resulting in cell cycle arrest (Jedinak et al, 2011;Sliva et al, 2012;WHO, 2014;Wu et al, 2013). Apoptosis of cancer cell lines was also observed after treatment with G. lucidum triterpenes and Fukuzawa et al (2008) and Tang et al (2006) demonstrated that apoptosis is triggered by the increase of pro-apoptotic proteins and decrease of anti-apoptotic proteins.…”

Ganoderma lucidum on the inhibition of colorectal cancer

“…All suppression functions were enhanced by high dosages of triterpene extract. In conclusion, Sliva's work has confirmed that triterpene extract is able to suppress colon inflammation and prevent tumor incidence and tumor multiplicity [37].…”

“…While the autophagy was medicated through the inhibition of P38 MAPK, the triterpene extract was able to suppress phosphorylation of P38 MAPK [39]. The group has further shown that the triterpene extract was able to down regulate PHIP/DSS-dependent expression of cyclin D1, COX-2, CYP1A2 and CYP3A4 in colon tissue and affect activities of transcription regulator of metabolic enzymes in vitro and modulates expression of CYP1A2, 4 and 1 in vivo [37].…”