Cucurbitacin E exhibits anti-inflammatory effect in RAW 264.7 cells via suppression of NF-κB nuclear translocation
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Cucurbitacin E (CuE), a triterpenoid compound isolated from Cucurbitaceae plants, possesses a wide range of biological activities including anti-inflammatory properties. The present study aimed to investigate the anti-inflammatory effect of CuE and the underlying mechanism of action.
The anti-inflammatory effect of CuE was evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Cell proliferation was assessed using a modified MTT assay. Cell cycle distribution was analyzed by propidium iodide staining. The actin cytoskeleton was examined by immunofluorescent staining. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β was determined by intracellular cytokine staining. G-actin level and nuclear factor (NF)-κB nuclear translocation were detected by immunoblotting.
CuE inhibited cell proliferation and induced cell cycle arrest at G2/M phase in RAW 264.7 cells. CuE also suppressed LPS-induced cell spreading and pseudopodia formation. These effects were associated with decreased G-actin level and severe actin aggregation. Moreover, CuE significantly inhibited both TNF-α and IL-1β production in LPS-stimulated RAW 264.7 cells. This was likely mediated by suppressing LPS-induced nuclear translocation of NF-κB, a critical transcription factor responsible for pro-inflammatory cytokine expression.
CuE displayed anti-inflammatory effects through suppression of NF-κB nuclear translocation leading to a decreased expression of TNF-α and IL-1β in LPS-stimulated RAW 264.7 cells.
KeywordsCucurbitacin E RAW 264.7 cells Lipopolysaccharides Actin cytoskeleton NF-κB
This work is supported by grants from the National Natural Science Foundation of China (No.81173604), the Specialized Research Program of “Twelfth Five-Year Plan” of China (No.2011ZX09307-303-03), and the Fundamental Research Funds for the Central Universities (No.21612411).
- 2.Dong Y, Lu B, Zhang X, Zhang J, Lai L, Li D, Wu Y, Song Y, Luo J, Pang X, Yi Z, Liu M. Cucurbitacin E, a tetracyclic triterpenes compound from Chinese medicine, inhibits tumor angiogenesis through VEGFR2-mediated Jak2-STAT3 signaling pathway. Carcinogenesis. 2010;31:2097–104.PubMedCrossRefGoogle Scholar
- 5.Abdelwahab SI, Hassan LE, Sirat HM, Yagi SM, Koko WS, Mohan S, Taha MM, Ahmad S, Chuen CS, Narrima P, Rais MM, Hadi AH. Anti-inflammatory activities of cucurbitacin E isolated from Citrullus lanatus var. citroides: role of reactive nitrogen species and cyclooxygenase enzyme inhibition. Fitoterapia. 2011;82:1190–7.PubMedCrossRefGoogle Scholar
- 8.Karin M, Staudt L. NF-κB a network hub controlling immunity, inflammation, and cancer: a subject collection from Cold Spring Harbor perspectives in biology. Cold Spring Harbor, Cold Spring Harbor Laboratory Press, NY; 2010. viii, p 271.Google Scholar
- 10.Liou H-C. NF-κB/Rel transcription factor family. Georgetown, Tex. New York: Landes Bioscience/Eurekah.com, Springer Science+Business Media, 2006. p 185.Google Scholar
- 20.Sorensen PM, Iacob RE, Fritzsche M, Engen JR, Brieher WM, Charras G. Eggert US. ACS Chem Biol: The natural product cucurbitacin E inhibits depolymerization of actin filaments; 2012.Google Scholar
- 22.Huang WW, Yang JS, Lin MW, Chen PY, Chiou SM, Chueh FS, Lan YH, Pai SJ, Tsuzuki M, Ho WJ, Chung JG. Cucurbitacin E induces G(2)/M phase arrest through STAT3/p53/p21 signaling and provokes apoptosis via Fas/CD95 and mitochondria-dependent pathways in human bladder cancer T24 cells. Evid Based Complement Alternat Med. 2012;2012:952762.PubMedGoogle Scholar