title: Chemosensitizing effect of Paris Saponin I on Camptothecin and 10-hydroxycamptothecin in lung cancer cells via p38 MAPK, ERK, and Akt signaling pathways.
abstract: Paris Saponin I (PSI), a steroidal sponins isolated from plant, has been exhibited antitumor and many other biological activities. In this study, we investigated the role and underlying mechanisms of PSI in the synergistic regulation of antitumor activity of Camptothecin (CPT) and 10-hydroxycamptothecin (HCPT) in four types of lung cancer cells. The inhibitory evaluation showed that PSI could significantly reduce the CPT/HCPT-mediated cell proliferation and enhance the sensitivities of H1299, H460 and H446 lung cancer cells to CPT/HCPT. Mechanism study indicated that PSI improved the CPT/HCPT induced apoptosis in lung cancer cells through mitochondria pathway including cytochrome C release and activation of caspase-9 and -3 cascades. Furthermore, PSI plus CPT/HCPT also increased the up-regulation of Bax and down-regulation of Bcl-2 and Bcl-XL in H460 and H446 cells. Moreover, PSI enhanced CPT/HCPT-mediated inhibition of p38 MAPK and activation of phosphorylation of p38 MAPK in H1299 cells, and suppression of Akt and ERK pathways activation in H460 cells as well as in H446 cells. Collectively, our results demonstrated that PSI functions as a chemosensitizer by enhancing apoptosis through influencing p38 MAPK, ERK, and Akt pathways in lung cancer cells, and the combination with CPT/HCPT might be a promising strategy for the development of new therapeutic agents.
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Wenzhu
authors.initials: W
authors.lastname: Chen
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Pan
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Xuzhe
authors.initials: X
authors.lastname: Li
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Man
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Yuou
authors.initials: Y
authors.lastname: Teng
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China. Electronic address: yupeng@tust.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address: pharmgao@tju.edu.cn.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Gao
mesh_terms: D015153:Blotting, Western; D002166:Camptothecin / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D020935:MAP Kinase Signaling System; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012503:Saponins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D012503:Saponins; C121203:polyphyllin D; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D004144:Diosgenin; D002166:Camptothecin
keywords: 10-Hydroxycamptothecin; Akt; Camptothecin; ERK; Lung cancer cells; Paris Saponin I; p38 MAPK