title: A soft coral natural product, 11-episinulariolide acetate, inhibits gene expression of cyclooxygenase-2 and interleukin-8 through attenuation of calcium signaling.
abstract: Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancer cells. EGFR-mediated signaling involves inflammatory gene expression including cyclooxygenase (COX)-2 and interleukin (IL)-8, and is associated with cancer pathogenesis. In a search of phytochemicals with anti-inflammatory activity, the COX-2 and IL-8 inhibitory activities of some marine compounds were examined. After screening these compounds 11-episinulariolide acetate (1) from soft coral exhibited the most potent activity. Reverse-transcription PCR; western blotting; ELISA and luciferase assays were used to test the effect of compound 1 on EGF-stimulated expressions of COX-2 and IL-8 in A431 human epidermoid carcinoma cells. After exposure to 10 μM of compound 1, expression levels of COX-2 and IL-8 were reduced. In addition; intracellular Ca²⁺ increase and Ca²⁺-dependent transcription factor activation were blocked by compound 1. Thus, compound 1 can potentially serve as a lead compound for targeting Ca²⁺ signaling-dependent inflammatory diseases.
authors.affiliation: Department of Clinical Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Hsu
authors.forename: Siou-Jin
authors.initials: SJ
authors.lastname: Chiu
authors.forename: Yao-Ting
authors.initials: YT
authors.lastname: Tsai
authors.forename: Che-Mai
authors.initials: CM
authors.lastname: Chang
authors.forename: Jaw-Yan
authors.initials: JY
authors.lastname: Wang
authors.forename: Eric Terry
authors.initials: ET
authors.lastname: Wang
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hou
authors.forename: Chiung-Yao
authors.initials: CY
authors.lastname: Huang
authors.forename: Jyh-Horng
authors.initials: JH
authors.lastname: Sheu
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
mesh_terms: D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001688:Biological Products; D052246:Cyclooxygenase 2 Inhibitors; D004224:Diterpenes; D016209:Interleukin-8; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D004815:Epidermal Growth Factor; C050253:sinulariolide; D051546:Cyclooxygenase 2