title: In vitro and in vivo antitumour activities of puerarin 6″-O-xyloside on human lung carcinoma A549 cell line via the induction of the mitochondria-mediated apoptosis pathway.
abstract: Context Pueraria lobata (Leguminoseae) shows cytotoxic effects against cancer cells; however, its active components remain unclear. Objective This study investigated the antitumour activity of puerarin 6″-O-xyloside (POS) on the human lung carcinoma A549 cell line. Materials and methods The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the cytotoxicity of POS (at 10, 20 and 40 μM) in vitro, and xenograft nude mice were established to evaluate the antitumour effect of POS (at 40 mg/kg/d) in vivo by 15 days intraperitoneal injection (ip). To explore its mechanism of action, flow cytometry was performed to determine the pro-apoptotic effect of POS (at 10, 20 and 40 μM). Subsequently, the expression of caspase-3, caspase-7, caspase-9, Bcl-2 and Bax in A549 cells were determined. Results POS showed significant cytotoxicity toward A549 cells (p < 0.05) by inducing apoptosis. Treatment with POS significantly upregulated the levels of caspase-3 (p < 0.01), caspase-7 (p < 0.01), caspase-9 (p < 0.01) and Bax (p < 0.01) in A549 cells, and Bcl-2 was downregulated (p < 0.01). Additionally, the in vivo animal study showed that POS significantly inhibited tumour growth in A549 cells (p < 0.01). Conclusion Our study demonstrated the POS has significant antitumour activities. The mechanisms are related to increased levels of caspase-3, caspase-7, caspase-9 and Bax, and reduced levels Bcl-2.
authors.affiliation: a Department of Oncology , Changshu No. 1 People's Hospital , Changshu , PR China.
authors.forename: Ti
authors.initials: T
authors.lastname: Chen
authors.affiliation: a Department of Oncology , Changshu No. 1 People's Hospital , Changshu , PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: a Department of Oncology , Changshu No. 1 People's Hospital , Changshu , PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a Department of Oncology , Changshu No. 1 People's Hospital , Changshu , PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D006027:Glycosides; D007529:Isoflavones; C000610752:puerarin 6'-O-xyloside
keywords: Bcl-2; Pueraria lobata; caspase; xenograft model in nude mice