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.
Highlights
Epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase superfamily that is overexpressed in different types of cancers, is associated with tumor malignancy [1]
The application of compound 1 resulted in the reduction of COX-2 (Figure 2A) and IL-8 (Figure 2B)
The protein levels of COX-2 and IL-8 displayed similar results (Figure 2C,D). To further confirm these results, COX-2 and IL-8 promoter activities were analyzed by constructing a full-length promoter into the luciferase reporter plasmid, as described in the panels of (Figure 2E,F)
Summary
Epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase superfamily that is overexpressed in different types of cancers, is associated with tumor malignancy [1]. The expression of COX-2 can be triggered by EGF or histamine in cancer cells [4,5]. IL-8 is known to induce matrix metalloproteinase (MMP)-9 release, which further regulates tumor cell proliferation, angiogenesis, invasion, and metastatic dissemination [10,11]. Both COX-2 and IL-8 can be mediated by intracellular. EGF-mediated COX-2 and IL-8 expressions in cancer cells. Our findings provide evidence to support the functional inhibitory activity of compound 1 on cytoplasmic calcium concentration COX-2 and IL-8.
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