title: Cold-water extracts of Grifola frondosa and its purified active fraction inhibit hepatocellular carcinoma in vitro and in vivo.
abstract: Mushrooms are used in traditional Chinese medicine to treat a variety of diseases. Grifola frondosa (GF) is an edible mushroom indigenous to many Asian countries with a large fruiting body characterized by overlapping caps. In particular, GF is known for its anti-tumor activity, which has been targeted by scientific and clinical research. This study aimed to investigate the effects of the cold-water extract of GF (GFW) and its active fraction (GFW-GF) on autophagy and apoptosis, and the underlying mechanisms in vitro and in vivo Our results revealed that GFW and GFW-GF inhibited phosphatidylinositol 3-kinase (PI3K) and stimulated c-Jun N-terminal kinase (JNK) pathways, thereby inducing autophagy. We also demonstrated that GFW and GFW-GF inhibited proliferation, induced cell cycle arrest, and apoptosis in Hep3B hepatoma cells. GFW and GFW-GF markedly arrested cells in S phase and promoted cleavage of caspase-3 and -9. In addition, GFW and GFW-GF decreased the expression levels of the anti-apoptotic proteins protein kinase B and extracellular signal-regulated kinase. We also found that GFW significantly inhibited tumor growth in nude mice implanted with Hep3B cells. Our work demonstrates that GF and its active fraction inhibit hepatoma growth by inducing autophagy and apoptosis.
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Biotechnology, Asia University, Taichung 41354, Taiwan.
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan krlee@mx.nthu.edu.tw leiwan@mail.cmu.tw lei.joseph@gmail.com.
authors.forename: Kuan-Rong
authors.initials: KR
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, China Medical University Hospital, Taichung 40402, Taiwan School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan Department of Gynecology, China Medical University Hospital, Taichung 40402, Taiwan.
authors.forename: Wu-Chou
authors.initials: WC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Ter-Hsin
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Department of Biotechnology, Asia University, Taichung 41354, Taiwan School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan Department of Gynecology, China Medical University Hospital, Taichung 40402, Taiwan.
authors.forename: Lei
authors.initials: L
authors.lastname: Wan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045424:Complex Mixtures / Q000302:isolation & purification / Q000494:pharmacology*; D048691:Grifola / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008819:Mice, Nude
chemical_list: D045424:Complex Mixtures
keywords: Grifola frondosa; Hep3B; apoptosis; autophagy; bioactive; cell cycle