A Soft Coral Natural Product 11-Episinulariolide Acetate Inhibits Gene Expression of Cyclooxygenase-2 and Interleukin-8 through Attenuation of Calcium Signaling

摘要

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.