title: Elucidating the inhibitory mechanisms of the ethanolic extract of the fruiting body of the mushroom Antrodia cinnamomea on the proliferation and migration of murine leukemia WEHI-3 cells and their tumorigenicity in a BALB/c allograft tumor model.
abstract: The aim of this study was to explore whether the ethanolic extract of Antrodia cinnamomea (EEAC), a medical mushroom form Taiwan, could affect the proliferation and migration of WEHI-3 cells in vitro and to explore the antitumor effects of EEAC in BALB/c mice engrafted with WEHI-3 cells. The results showed that EEAC inhibited the proliferation of WEHI-3 cells, resulting in the accumulation of cell in G0/G1 and G2/M phases, as determined by flow cytometry. Moreover, EEAC markedly reduced the migration of WEHI-3 cells, as determined by a transwell assay. Treatment of WEHI-3 cells with EEAC also decreased MMP-9 protein expression and enzyme activity. The protein levels of p-Akt, p-ERK1/2 were also decreased, whereas the expression of p21 and p27 was increased. Furthermore, in an in vivo model, EEAC treatment reduced the infiltration of WEHI-3 cells into the liver and spleens and decreased tumor growth. Other bioactive compounds, such as cordycepin and zhankuic acid A, have been demonstrated to reduce the expression of MMP-9, cyclin E, cyclin D1 and to increase the expression of p21, p27. This is the first study to investigate that the mechanisms by which EEAC reduce the proliferation and migration of WEHI-3 cells in vitro, as well as the ability of EEAC to reduced infiltration of WEHI-3 cells into the liver and spleen in vivo. The results suggest that EEAC may prove to be useful in future antileukemic therapies.
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Fon-Chang
authors.initials: FC
authors.lastname: Liu
authors.forename: Ming-Tsung
authors.initials: MT
authors.lastname: Lai
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Chen
authors.forename: Wen-Hsin
authors.initials: WH
authors.lastname: Lin
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chang
authors.forename: Ming-Jyh
authors.initials: MJ
authors.lastname: Sheu
authors.forename: Chieh-Hsi
authors.initials: CH
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D055491:Antrodia; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D048690:Fruiting Bodies, Fungal / Q000737:chemistry* / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents
keywords: Antileukemic; Antrodia cinnamomea; Migration; Mushroom; Proliferation; WEHI-3 cells