title: Blackberry extracts inhibit activating protein 1 activation and cell transformation by perturbing the mitogenic signaling pathway.
abstract: Blackberries are natural rich sources of bioflavonoids and phenolic compounds that are commonly known as potential chemopreventive agents. Here, we investigated the effects of fresh blackberry extracts on proliferation of cancer cells and neoplastic transformation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as well as the underlying mechanisms of signal transduction pathways. Using electron spin resonance, we found that blackberry extract is an effective scavenger of free radicals, including hydroxyl and superoxide radicals. Blackberry extract inhibited the proliferation of a human lung cancer cell line, A549. Pretreatment of A549 cells with blackberry extract resulted in an inhibition of 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation induced by ultraviolet B (UVB) irradiation. Blackberry extract decreased TPA-induced neoplastic transformation of JB6 P+ cells. Pretreatment of JB6 cells with blackberry extract resulted in the inhibition of both UVB- and TPA-induced AP-1 transactivation. Furthermore, blackberry extract also blocked UVB- or TPA-induced phosphorylation of ERKs and JNKs, but not p38 kinase. Overall, these results indicated that an extract from fresh blackberry may inhibit tumor promoter-induced carcinogenesis and associated cell signaling, and suggest that the chemopreventive effects of fresh blackberry may be through its antioxidant properties by blocking reactive oxygen species-mediated AP-1 and mitogen-activated protein kinase activation.
authors.affiliation: Pathology and Physiology Research Branch, Helath Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
authors.forename: Rentian
authors.initials: R
authors.lastname: Feng
authors.forename: Linda L
authors.initials: LL
authors.lastname: Bowman
authors.forename: Yongju
authors.initials: Y
authors.lastname: Lu
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Leonard
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Jiang
authors.forename: Vince
authors.initials: V
authors.lastname: Castranova
authors.forename: Val
authors.initials: V
authors.lastname: Vallyathan
authors.forename: Min
authors.initials: M
authors.lastname: Ding
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D020929:Mitogen-Activated Protein Kinase Kinases; D013755:Tetradecanoylphorbol Acetate