title: Anti-tumor effect of polysaccharide from Hirsutella sinensis on human non-small cell lung cancer and nude mice through intrinsic mitochondrial pathway.
abstract: Our previous works had proved the structural properties of Hirsutella sinensis polysaccharide-III(HSP-III). Herein, its anti-tumor effect on lung cancer correlated with mitochondrial apoptosis pathway was investigated. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that HSP-III induces the apoptosis of H1299 cells; however the proliferation viability of normal lung epithelial cells is not affected. HSP-III treatment collapses the H1299 cell mitochondrial membrane potential, and western blot analysis of cytochrome C, Bax, caspase-3 and caspase-9 further indicates that apoptotic effects induced by HSP-III is through the mitochondrial pathway. Furthermore, we found the apoptotic effects of HSP-III are triggered by Reactive oxygen species (ROS) generation. Blue native Polyacrylamide Gel-Electrophoresis (PAGE) showed the expressions of mitochondrial respiratory chain complexes I-V were also decreased. Taken together, anti-tumor effect of HSP-III is through intrinsic mitochondrial apoptosis mechanism pathway and involving ROS increasing. Finally, in vivo nude mice experiment, HSP-III attenuated the growth of tumor compared with control. In contrast, N-acetyl-l-cysteine (NAC) could restore the cell apoptosis effects induced by HSP-III. These findings suggest that HSP-III induce apoptosis of H1299 cells and attenuated growth of nude mice tumor in vivo through the intrinsic mitochondrial pathway and stimulating ROS. HSP-III could be a composition for lung cancer treatment.
authors.affiliation: Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Science and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Liu
authors.affiliation: School of Medicine, Yunnan University, Kunming 650091, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xie
authors.affiliation: Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Science and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Hui-Qing
authors.initials: HQ
authors.lastname: Sun
authors.affiliation: Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Science and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Meng
authors.affiliation: Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Science and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address: zhyuanzhu@tust.edu.cn.
authors.forename: Zhen-Yuan
authors.initials: ZY
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001203:Ascomycota / Q000737:chemistry*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011134:Polysaccharides; D017382:Reactive Oxygen Species; D053148:Caspase 3; D053453:Caspase 9
keywords: Cell apoptosis; Mitochondrial pathway; Polysaccharide