title: Analysis on the mechanism of Helicobacter pylori-induced apoptosis in gastric cancer cell line BGC-823.
abstract: Helicobacter pylori (Hp) can induce apoptosis of gastric cancer cells. The mechanism of the process still needs further elucidating. This study was aimed to analyse the mechanism through which Hp induce apoptosis in human gastric cancer cell line BGC-823. The extract from VacA(+) and CagA(+) Helicobacter pylori strain NCTC11637 was applied to induce apoptosis. The expression, breakdown, and phosphorylation of proteins were probed by Western blotting with specific antibodies. Apoptosis of the cells was detected by flow cytometry. The results showed that incubating the cells with Hp extract caused the breakdown of both caspase-3 and -1. The breakdown was dose-dependent and correlated with the occurrence of the Hp extract-induced apoptosis. Among the substrates of caspase-3, DNA fragment factor (DFF) was degraded during incubation with Hp extract and a small fragment was released. However, poly(ADP-ribose) polymerase (PARP) did not break down during the incubation. Tyrosine kinase inhibitor Genistein prevented both the break down of caspase-3 and the apoptosis induced by Hp extract. MAPK/ERK inhibitor PD98059 did not prevent the apoptosis induced by Hp extract. The expression and activity of JNK, and the expression of Bcl-2 and Fas proteins did not change during the incubation with Hp extract. The results suggested that Hp extract initiated apoptosis in BGC-823 cells through activating tyrosine kinase, caspase-1, -3, and DFF.
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212001, PR China. ycchen54@ujs.edu.cn
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenrong
authors.initials: W
authors.lastname: Xu
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D019833:Genistein / Q000494:pharmacology; D016480:Helicobacter pylori / Q000737:chemistry*; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011506:Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D019014:fas Receptor
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; C491901:FAS protein, human; D005419:Flavonoids; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; C109664:caspase-activated DNase inhibitor; D019014:fas Receptor; D019833:Genistein; D011065:Poly(ADP-ribose) Polymerases; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one