title: Zanthoxylum avicennae extracts induce cell apoptosis through protein             phosphatase 2A activation in HA22T human hepatocellular carcinoma cells and block             tumor growth in xenografted nude mice.
abstract: The use of herbs as alternative cancer therapies has attracted a great deal of attention owing to their lower toxicity. Whether Zanthoxylum avicennae (Ying Bu Bo, YBB) induces liver cancer cell apoptosis remains unclear. In this study, we investigated the effect of YBB extracts (YBBEs) on HA22T human hepatocellular carcinoma cells in vitro and in an in vivo mouse xenograft model. HA22T cells were treated with different concentrations of YBBEs and analyzed with Western blot analysis, TUNEL, JC-1 staining and siRNA transfection assays. Additionally, the HA22T-implanted xenograft nude mice model was applied to confirm the cellular effects. YBBEs-induced apoptosis, up-regulated death receptor apoptotic pathway markers as well as mitochondrial proteins, and suppressed the survival proteins in a dose-dependent manner. Pro-survival Bcl-2 family proteins were inhibited and the pro-apoptotic ones were increased. Protein phosphatase 2A (PP2A) siRNA or okadaic acid reversed the YBBEs effects, confirming the role of PP2A in YBBEs-induced HA22T apoptosis. All our experimental evidence indicates that YBBEs significantly promote HA22T apoptosis and reduce tumor sizes in xenograft nude mice via PP2A in a dose-dependent manner.
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: Chung-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Wen-Huang
authors.initials: WH
authors.lastname: Peng
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; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D032106:Zanthoxylum / Q000737:chemistry*
chemical_list: D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D054648:Protein Phosphatase 2; D053148:Caspase 3