title: In vivo antitumor effects of 4,7-dimethoxy-5-methyl-1,3-benzodioxole isolated from the fruiting body of Antrodia camphorata through activation of the p53-mediated p27/Kip1 signaling pathway.
abstract: In this study, 4,7-dimethoxy-5-methyl-1,3-benzodioxole (SY-1) was isolated from three different sources of dried Antrodia camphorata (AC) fruiting bodies. AC is a medicinal mushroom that grows on the inner heartwood wall of Cinnamomum kanehirai Hay (Lauraceae), which is an endemic species that is used in Chinese medicine for its antitumor properties. We demonstrated that SY-1 [given as a 1-30 mg/kg body weight intraperitoneal (ip) injection three times per week] profoundly decreased the growth of COLO-205 human colon cancer cell tumor xenografts in an athymic nude mouse model. We further demonstrated that significant AC extract-mediated antitumor effects were observed at the highest concentration (5 g/kg body weight/day). No gross toxicity signs were observed (i.e., body weight changes, general appearance, or individual organ effects). Frozen COLO-205 xenograft tumors were pulverized in liquid N(2), and the expression of cell cycle regulatory proteins was detected by immunoblotting. We found that the p53-mediated p27/Kip1 protein was significantly induced in the low-dose (1 mg/kg body weight) SY-1-treated tumors, whereas the p21/Cip1 protein levels did not change. The G0/G1 phase cell cycle regulators induced by SY-1 were also associated with a significant decrease in cyclins D1, D3, and A. These results provide further evidence that SY-1 may have significance for cancer chemotherapy.
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Tu
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Chen
authors.forename: Ching-Shui
authors.initials: CS
authors.lastname: Huang
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Chien-Hsi
authors.initials: CH
authors.lastname: Chang
authors.forename: Hsiu-Man
authors.initials: HM
authors.lastname: Lien
authors.forename: Yuan-Soon
authors.initials: YS
authors.lastname: Ho
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D055491:Antrodia / Q000737:chemistry*; D052117:Benzodioxoles / Q000302:isolation & purification / Q000627:therapeutic use*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D048690:Fruiting Bodies, Fungal / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C574078:4,7-dimethoxy-5-methyl-1,3-benzodioxole; D000970:Antineoplastic Agents; D052117:Benzodioxoles; D018797:Cell Cycle Proteins; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27