Baicalein inhibits TNF-α-induced NF-κB activation and expression of NF-κB-regulated target gene products.
The nuclear factor-κB (NF-κB) transcription factors control many physiological processes including inflammation, immunity, apoptosis and angiogenesis. In our search for NF-κB inhibitors from natural resources, we identified baicalein from Scutellaria baicalensis as an inhibitor of NF-κB activation. As examined by the NF-κB luciferase reporter assay, we found that baicalein suppressed TNF-α-induced NF-κB activation in a dose-dependent manner. It also inhibited TNF-α-induced nuclear translocation of p65 through inhibition of phosphorylation and degradation of IκBα. Furthermore, baicalein blocked the TNF-α-induced expression of NF-κB target genes involved in anti-apoptosis (cIAP-1, cIAP-2, FLIP and BCL-2), proliferation (COX-2, cyclin D1 and c-Myc), invasion (MMP‑9), angiogenesis (VEGF) and major inflammatory cytokines (IL-8 and MCP1). The flow cytometric analysis indicated that baicalein potentiated TNF-α-induced apoptosis and induced G1 phase arrest in HeLa cells. Moreover, baicalein significantly blocked activation of p38, extracellular signal-regulated kinase 1/2 (ERK1/2). Our results imply that baicalein could be a lead compound for the modulation of inflammatory diseases as well as certain cancers in which inhibition of NF-κB activity may be desirable.
Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, P.R. China.
Junbo
J
Li
Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, P.R. China.
Juan
J
Ma
Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, P.R. China.
Ke Si
KS
Wang
Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, P.R. China.
Chunliu
C
Mi
Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, P.R. China.
Zhe
Z
Wang
Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, P.R. China.
Lian Xun
LX
Piao
Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, P.R. China.
Guang Hua
GH
Xu
Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, P.R. China.
Xuezheng
X
Li
Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, P.R. China.
Jung Joon
JJ
Lee
Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, P.R. China.
Xuejun
X
Jin
D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D044950:Flavanones / Q000008:administration & dosage*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D010936:Plant Extracts / Q000008:administration & dosage*; D031364:Scutellaria baicalensis; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics
D044950:Flavanones; D016328:NF-kappa B; D009363:Neoplasm Proteins; D010936:Plant Extracts; C498143:RELA protein, human; C499814:Scutellaria baicalensis extract; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C006680:baicalein; D051550:I-kappa B Kinase; D048051:p38 Mitogen-Activated Protein Kinases