Abstract
BackgroundA greater reduction in cancer risk associated with mushroom diet rich in fungus polysaccharides is generally accepted. Meanwhile, edible Pleurotus abalonus as a member of Abalone mushroom family is a popular nutritional supplement that purportedly prevents cancer occurrence. However, these anecdotal claims are supported by limited studies describing tumor-inhibitory responses to the promising polysaccharides, and the molecular mechanisms underlying these properties have not yet been elucidated.Methodology/Principal FindingsWe here fractionated the crude polysaccharide preparation from the fruiting bodies of P. abalonus into three fractions, namely PAP-1, PAP-2 and PAP-3, and tested these fractions for antiproliferative activity in human breast cancer MCF-7 cells. The largest PAP-3, an acidic polysaccharide fraction with a molecular mass of 3.68×105 Da, was the most active in inhibiting MCF-7 cancer cells with an IC50 of 193 µg/mL. The changes in cell normal morphology were observed by DAPI staining and the PAP-3-induced apoptosis was confirmed by annexin V/propidium iodide staining. The apoptosis was involved in mitochondria-mediated pathway including the loss of mitochondrial membrane potential (Δψm), the increase of Bax/Bcl-2 ratio, caspase-9/3 activation, and poly(ADP-ribose) polymerase (PARP) degradation, as well as intracellular ROS production. PAP-3 also induced up-regulation of p53, and cell cycle arrest at the S phase. The incubation of MCF-7 cells with antioxidant superoxide dismutase (SOD) and N-acetylcysteine (NAC) significantly attenuated the ROS generation and apoptosis caused by PAP-3, indicating that intracellular ROS plays a pivotal role in cell death.Conclusions/SignificanceThese findings suggest that the polysaccharides, especially acidic PAP-3, are very important nutritional ingredients responsible for, at least in part, the anticancer health benefits of P. abalonus via ROS-mediated mitochondrial apoptotic pathway. It is a major breakthrough bringing new insight of the potential use of the polysaccharides as health-care food or medicine to provide significant natural defense against human cancer.
Highlights
Mushroom is a special group of macroscopic fungi with distinctive and visible fruiting body that may grow above or below ground, and many mankind cultures have used mushrooms as a food and medicine since ancient times [1], [2]
Our results demonstrate that high-molecular mass of PAP-3 is more active in inhibiting the growth of MCF-7 cells, and the effect of the PAP3 is associated with reactive oxygen species (ROS) production leading to mitochondrial dysfunction, causing cancer cell death
PAP-1 eluted with deionized water was known as the neutral polysaccharides, whereas PAP-2 and PAP-3 eluted with 0.05 M and 0.1 M NaCl were known as acidic polysaccharides [27]
Summary
Mushroom is a special group of macroscopic fungi with distinctive and visible fruiting body that may grow above or below ground, and many mankind cultures have used mushrooms as a food and medicine since ancient times [1], [2] In this regard, edible mushrooms have been strongly investigated because naturally occurring wide varieties make up a high proportion in our diet owing to their attractive taste, aroma and nutritional values, and are found to contain large amounts of putative bioactive compounds with their health benefits [3], [4]. Edible Pleurotus abalonus as a member of Abalone mushroom family is a popular nutritional supplement that purportedly prevents cancer occurrence These anecdotal claims are supported by limited studies describing tumor-inhibitory responses to the promising polysaccharides, and the molecular mechanisms underlying these properties have not yet been elucidated
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