Research Papers:

Casticin inhibits interleukin-1β–induced ICAM-1 and MUC5AC expression by blocking NF-κB, PI3K-Akt, and MAPK signaling in human lung epithelial cells

Chian-Jiun Liou and Wen-Chung Huang _

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Oncotarget. 2017; 8:101175-101188. https://doi.org/10.18632/oncotarget.20933

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Chian-Jiun Liou1,2 and Wen-Chung Huang2,3

1Department of Nursing, Chang Gung University of Science and Technology, Taoyuan City, 33303, Taiwan

2Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan City, 33303, Taiwan

3Graduate Institute of Health Industry Technology, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City, 33303, Taiwan

Correspondence to:

Wen-Chung Huang, email: [email protected]

Keywords: casticin, ICAM-1, Interleukin-1β, MAPK, NF-κB

Received: June 30, 2017     Accepted: August 27, 2017     Published: September 15, 2017


The compound casticin, isolated from Vitex rotundifolia, exerts anti-inflammatory effects and causes apoptosis of cancer cells. In this study, we explored the anti-inflammatory effects of casticin and modulation of cyclooxygenase (COX)-2, intercellular adhesion molecule 1 (ICAM-1), and mucin 5AC (MUC5AC) expression in interleukin-1β (IL-1β)–activated A549 human pulmonary epithelial cells. A549 cells were treated with various concentrations of casticin (5–20 μM), and an inflammatory response was triggered with interleukin (IL)-1β cytokines. Casticin decreased levels of IL-6, tumor necrosis factor α, and IL-8 and suppressed COX-2 expression and prostaglandin E2 production. It also reduced MUC5AC, proinflammatory cytokine, and chemokine gene expression and inhibited ICAM-1 expression for monocyte adhesion in IL-1β–stimulated A549 cells. In addition, casticin inhibited phosphorylation of Akt, phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) and blocked nuclear transcription factor kappa-B (NF-κB) subunit p65 protein translocation into the nucleus. Co-culture of NF-κB, MAPK, and PI3K inhibitors with casticin also led to more significantly suppressed ICAM-1 expression in inflammatory A549 cells. These results provide evidence that casticin has an anti-inflammatory effect by blocking proinflammatory cytokine, chemokine, and ICAM-1 expression via suppression of the PI3K/Akt, NF-κB, and MAPK signaling pathways in IL-1β–stimulated inflammatory pulmonary epithelial cells.

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