title: Zanthoxylum avicennae extracts inhibit cell proliferation through protein             phosphatase 2A activation in HA22T human hepatocellular carcinoma cells in vitro             and in vivo.
abstract: Hepatocellular carcinoma is a common type of cancer that is usually associated             with poor prognosis. In this study, we examined the in vitro and in vivo mechanisms             of the traditional Vietnamese herb Zanthoxylum avicennae on the inhibition of             HA22T human hepatocellular carcinoma cell proliferation. HA22T cells were treated             with different concentrations of Zanthoxylum avicennae extracts (YBBEs) and analyzed             with the MTT assay, western blot analysis, flow cytometry, siRNA transfection             assays and co-immunoprecipitation assay. Additionally, the HA22T-implanted xenograft             nude mouse model was applied to confirm the cellular effects. YBBEs showed a strong             inhibition of HA22T cell viability in a dose-dependent manner and significantly             reduced cell proliferation-related proteins as well as induced cell cycle arrest             in the G2/M phase. Protein phosphatase 2A (PP2A) siRNA or okadaic acid totally             blocked YBBE-mediated cell proliferation inhibition. In addition, an HA22T-implanted             nude mouse model further confirmed that YBBEs inhibit HA22T tumor cell growth             and downregulate the survival and cell cycle regulating proteins, as well as activate             the PP2A protein. Our findings indicate that the inhibition of HA22T cell proliferation             by YBBEs is mediated through PP2A activation.
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Tran Duc
authors.initials: TD
authors.lastname: Dung
authors.forename: Hsien-Cheh
authors.initials: HC
authors.lastname: Chang
authors.forename: Truong Viet
authors.initials: TV
authors.lastname: Binh
authors.forename: Maw-Rong
authors.initials: MR
authors.lastname: Lee
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.forename: Li-Mien
authors.initials: LM
authors.lastname: Chen
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D032106:Zanthoxylum / Q000737:chemistry*
chemical_list: D010936:Plant Extracts; D034741:RNA, Small Interfering; D019319:Okadaic Acid; D051057:Proto-Oncogene Proteins c-akt; D054648:Protein Phosphatase 2