title: Pleurotus nebrodensis polysaccharide(PN50G) evokes A549 cell apoptosis by the ROS/AMPK/PI3K/AKT/mTOR pathway to suppress tumor growth.
abstract: Since the strong antineoplastic potential against A549 cells of Pleurotus nebrodensis polysaccharide (PN50G) in vitro has been proven previously, the definitive mechanism of PN50G-induced apoptosis in A549 cells in vivo was further investigated. All the results indicated that PN50G significantly suppressed tumor growth in A549 tumor-bearing mice. Tumor cells treated with PN50G were arrested in the G0/G1 phase, and marked changes in the expression of cell cycle-related proteins, including cyclin D1, cyclin A and cyclin B1, were observed. Moreover, western blotting analysis indicated that PN50G triggered the mitochondrial apoptotic pathway, for an increased Bax/Bcl-2 ratio, release of cytochrome c, cleavage of caspase-3 and PRPP in A549 tumor cells were observed. And the decrease in the expression of the translation related protein P70S6K was observed, because PN50G activated AMPK phosphorylation, but inhibited PI3K/AKT phosphorylation and suppressed the activation of the mammalian target of rapamycin (mTOR) induced by PN50G. In vivo imaging was performed on tumor-bearing mice, and the results indicated that PN50G significantly increased the intracellular levels of reactive oxygen species (ROS). Furthermore, it indicated that PN50G promoted the protein expression of Beclin 1 and LC-3 in a dose-dependent manner. All the results suggested that PN50G-mediated apoptosis and autophagy of A549 tumor cells in vivo mainly involved in the mitochondrial pathway and the AMPK/PI3K/mTOR pathway.
authors.affiliation: Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. clw123@tust.edu.cn.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Cui
authors.affiliation: Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. clw123@tust.edu.cn.
authors.forename: Shufen
authors.initials: S
authors.lastname: Wu
authors.affiliation: Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. clw123@tust.edu.cn.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Shang
authors.affiliation: Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. clw123@tust.edu.cn.
authors.forename: Zhenjing
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. clw123@tust.edu.cn.
authors.forename: Mianhua
authors.initials: M
authors.lastname: Chen
authors.affiliation: Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. clw123@tust.edu.cn.
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Li
authors.affiliation: Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. clw123@tust.edu.cn.
authors.forename: Changlu
authors.initials: C
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D020076:Pleurotus / Q000737:chemistry*; D011134:Polysaccharides / Q000008:administration & dosage*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D055372:AMP-Activated Protein Kinases; D000970:Antineoplastic Agents; D019869:Phosphatidylinositol 3-Kinases; D011134:Polysaccharides; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human