In vitro antitumor effects of the cold-water extracts of Pleurotus eryngii var ferulae and Pleurotus nebrodensis on human colon cancer cells

Abstract

For centuries, mushrooms have been used as folk medicines especially in Asian countries where their medicinal properties are well known. On the basis of numerous experimental evidences collected in the last decades, the immunomodulatory and anti-neoplastic properties of substances extracted from various species belonging to genera of edible mushrooms [Agaricus L., Auricularia Bull. ex Juss., Ganoderma P. Karst., Grifola Gray, Lentinus Fr., Schizophyllum Fr., Tremella Dill ex L., etc.] are extensively recognized also at scientific levels. Several works have demonstrate that anti-cancer property of these molecules is due to their ability to enhance immune system activity and/or to act directly on cancer cells. Polysaccharides are responsible of a remarkable antitumor activity in vivo and many authors demonstrated their action through screening against sarcoma 180 in mice with an intraperitoneal or oral methods of administration (Ikekawa et al., 1969; Mori et al., 1986; Mizuno et al., 1995, Wasser & Weis, 1997). Among the well-studied medicinal mushrooms there are those belonging to the genus Pleurotus (Fr.) P. Kumm., one of the widely cultivated edible mushroom. Most of them are cultivated and provide a relatively cheap food of high dietetic value through rather simple solid-state fermentation processes. In addition, Pleurotus biomass demonstrates significant medicinal effects and its bioactive compounds possess antibiotic, antitumor, hypocholesterolemic and immunomodulation properties (Gunde-Cimerman, 1999; Babitskatya et al., 2000; Gunde-Cimerman & Plemenitas, 2001; Wasser, 2002; Zhang et al., 2004; Chang, 2006; Tsai et al., 2009). Most of researches concerning the anti-tumor properties of Pleurotus spp. have been carried out by testing the methanol/ethanol/ hot water extracts of Pleurotus ostreatus (Jacq.) P. Kumm. in several in vivo and in vitro cancer models. These studies provided interesting data supporting the possibility to isolate new therapeutic agents from this mushroom, but much less is known about the biological activities of extracts from other species of genus Pleurotus. Species like P. eryngii (DC.) Quél. var. ferulae (Lanzi) Sacc. and P. nebrodensis (Inzenga) Quél. are typical Mediterranean mushrooms and are particularly popular as choice edible mushrooms (Gargano et al., 2011 Zervakis, 2001). The aim of the present research was to evaluate whether the cold-water extract of P. eryngii var. ferulae (CWE-Pef) and P. nebrodensis (CWE-Pn) can affect the tumor phenotype of human colon cancer cells. Our result demonstrate that CWE-Pef and CWE-Pn inhibited the growth of HCT116 colon cancer cells by inducing apoptosis, promoted cancer cells aggregation and inhibited the adhesion of tumor cells to endothelial cells. Furthermore, both extracts inhibited tyrosine phosphorylation signaling as well as ERK phosphorylation. These effects were specific for tumor cells since no effects were observed on non-tumor cells. Finally, our data indicated that the active compounds may be protein/peptide compounds since high temperature treatment of CWE-Pef and CWE-Pn completely eliminated their anti-proliferative activity.