title: Dihydroartemisinin induces apoptosis in human gastric cancer cell line BGC-823 through activation of JNK1/2 and p38 MAPK signaling pathways.
abstract: Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, is associated with a broad range of biological properties including antitumor activity. However, the effect of DHA on gastric cancer has not been clearly clarified. The aim of this study was to investigate the role and mechanism of DHA in human gastric cancer cell line BGC-823. Cell viability was assessed by MTT assay. Cell apoptosis was analyzed with flow cytometry. The expressions of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK) and their phosphorylated forms as well as apoptosis related proteins were examined by western blot analysis. The results demonstrated that DHA inhibited cell viability of BGC-823 cells in a dose- and time-dependent manner. DHA treatment upregulated the expression of Bax, cleaved caspase-3 and -9, and degraded form of PARP, and downregulated the Bcl-2 expression and Bcl-2/Bax ratio. Meanwhile, DHA increased the phosphorylation of ERK1/2, JNK1/2 and p38 MAPK. Synthetic inhibitors of JNK1/2 or p38 MAPK kinase activity, but not inhibitor of ERK1/2, significantly abolished the DHA-induced activation of caspase-3 and -9. In vivo tumor-suppression assay further indicated that DHA displayed significant inhibitory effect on BGC-823 xenografts in tumor growth. These results indicate that DHA induces apoptosis of BGC-823 cells through JNK1/2 and p38 MAPK signaling pathways and DHA could serve as a potential additional chemotherapeutic agent for treatment of gastric cancer.
authors.affiliation: a Endoscopy Center, Tianjin Union Medicine Center , Tianjin , China.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: a Endoscopy Center, Tianjin Union Medicine Center , Tianjin , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: a Endoscopy Center, Tianjin Union Medicine Center , Tianjin , China.
authors.forename: Hongwen
authors.initials: H
authors.lastname: Ma
authors.affiliation: a Endoscopy Center, Tianjin Union Medicine Center , Tianjin , China.
authors.forename: Hongzhou
authors.initials: H
authors.lastname: Li
authors.affiliation: a Endoscopy Center, Tianjin Union Medicine Center , Tianjin , China.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Endoscopy Center, Tianjin Union Medicine Center , Tianjin , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: a Endoscopy Center, Tianjin Union Medicine Center , Tianjin , China.
authors.forename: Qiaoping
authors.initials: Q
authors.lastname: Wang
authors.affiliation: a Endoscopy Center, Tianjin Union Medicine Center , Tianjin , China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D037621:Artemisinins; C039060:artenimol; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Apoptosis; JNK1/2; dihydroartemisinin; gastric cancer; p38 MAPK