title: Involvement of the antioxidative property of morusin in blocking phorbol ester-induced malignant transformation of JB6 P+mouse epidermal cells.
abstract: Chemoprevention has been acknowledged as an important and practical strategy for managing cancer. We have previously synthesized morusin, a prenylated flavonoid that exhibits anti-cancer progression activity. In the present study, we evaluated the anti-cancer promotion potential of morusin by using the mouse epidermal JB6 P+cell model. Extensive evidence shows that tumor promotion by phorbol esters is due to the stimulation of reactive oxygen species (ROS). Therefore, the effect of morusin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ROS production was assessed. Noncytotoxic concentrations of morusin were found to dose-dependently reduce TPA-induced ROS production. Moreover, morusin inhibited TPA-induced activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) activation, which can mediate cell proliferation and malignant transformation. Furthermore, morusin inhibited the TPA upregulation of cyclooxygenase 2 (COX-2), which may be regulated by AP-1 and NF-κB. In addition, noncytotoxic concentrations of morusin reduced the TPA-promoted cell growth of JB6 P+cells and inhibited TPA-induced malignant properties, such as cytoskeletal rearrangement and cell migration of JB6 P+cells. Similar to the effects of glutathione (GSH) pretreatment, morusin inhibited TPA-induced expression of N-cadeherin and vimentin, which are malignant cell surface proteins. Finally, morusin treatment dose-dependently suppressed the TPA-induced anchorage-independent cell transformation of JB6 P+cells. In conclusion, our results evidence that morusin possesses anti-cancer promotion potential because of its antioxidant property, which mediates multiple transformation-associated gene expression.
authors.affiliation: Department of Dermatology, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Pai-Shan
authors.initials: PS
authors.lastname: Cheng
authors.affiliation: Department of Medical Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chao-Chin
authors.initials: CC
authors.lastname: Hu
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chau-Jong
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Department of Chemistry, National Changhua University of Education, Changhua, Taiwan.
authors.forename: Yean-Jang
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Medical Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Wei-Chia
authors.initials: WC
authors.lastname: Chung
authors.affiliation: Department of Medical Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Education, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address: tht@csmu.edu.tw.
authors.forename: Tsui-Hwa
authors.initials: TH
authors.lastname: Tseng
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002273:Carcinogens; D005419:Flavonoids; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; C057451:morusin; D051546:Cyclooxygenase 2; D013755:Tetradecanoylphorbol Acetate
keywords: JB6 P(+) cells; Morusin; TPA; Transformation