title: Xanthatin induces G2/M cell cycle arrest and apoptosis in human gastric carcinoma MKN-45 cells.
abstract: Xanthatin, a natural bioactive compound of sesquiterpene lactones, was isolated and purified from air-dried aerial part of Xanthium sibiricum Patrin ex Widder. In the present study, we demonstrated the significant antiproliferative and proapoptotic effects of xanthatin on human gastric carcinoma MKN-45 cells. MTS assay showed that xanthatin produced obvious cytotoxicity in MKN-45 cells with IC50 values of 18.6, 9.3, and 3.9 µM for 12, 24, and 48 h, respectively. Results of flow cytometry analysis indicated that the antiproliferative activity induced by xanthatin might be executed via G2/M cell cycle arrest and proapoptosis in MKN-45 cells. Western blot analysis elucidated that: a) xanthatin downregulated expression of Chk1 and Chk2 and phosphorylation of CDC2, which are known as key G2/M transition regulators; b) xanthatin increased p53 activation, decreased the bcl-2/bax ratio and the levels of downstream procaspase-9 and procaspase-3, which are key regulators in the intrinsic apoptosis pathway; c) xanthatin blocked phosphorylation of NF-κB (p65 subunit) and of IκBα, which might contribute to its proapoptotic effects on MKN-45 cells. In conclusion, our results suggest that xanthatin may have therapeutic potential against human gastric carcinoma.
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.forename: Junshan
authors.initials: J
authors.lastname: Ruan
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Wu
authors.forename: Linggeng
authors.initials: L
authors.lastname: Yan
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Fangtian
authors.initials: F
authors.lastname: Fan
authors.forename: Shizhong
authors.initials: S
authors.lastname: Zheng
authors.forename: Aiyun
authors.initials: A
authors.lastname: Wang
authors.forename: Yin
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D019926:Cyclin B / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D016158:Genes, p53; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D020128:Inhibitory Concentration 50; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D019926:Cyclin B; D005663:Furans; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051996:Transcription Factor RelA; D051028:bcl-2-Associated X Protein; D000072000:NF-KappaB Inhibitor alpha; C022186:xanthatin; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases