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

Molecules

Wen-Li Hsu²  Siou-Jin Chiu²  Yao-Ting Tsai²  Che-Mai Chang²  Jaw-Yan Wang¹  Eric Terry Wang²  Ming-Feng Hou¹  Chiung-Yao Huang³  Jyh-Horng Sheu⁴ 

[1] Division of Gastroeintestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan;Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan;Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan;Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan

关键词: marine compound;    EGF;    COX-2;    IL-8;    calcium;   

DOI  :  10.3390/molecules18067023

来源: mdpi

【 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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.