Attenuation of ERK/RSK2-driven NFκB gene expression and cancer cell proliferation by kurarinone, a lavandulyl flavanone isolated from Sophora flavescens ait. roots
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Attenuation of ERK/RSK2-driven NFκB gene expression and cancer cell proliferation by kurarinone, a lavandulyl flavanone isolated from Sophora flavescens ait. roots. / Berghe, Wim Vanden; De Naeyer, An; Dijsselbloem, Nathalie; David, Jean-Pierre; De Keukeleire, Denis; Haegeman, Guy.
In: ENDOCR METAB IMMUNE, Vol. 11, No. 3, 01.09.2011, p. 247-61.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Attenuation of ERK/RSK2-driven NFκB gene expression and cancer cell proliferation by kurarinone, a lavandulyl flavanone isolated from Sophora flavescens ait. roots
AU - Berghe, Wim Vanden
AU - De Naeyer, An
AU - Dijsselbloem, Nathalie
AU - David, Jean-Pierre
AU - De Keukeleire, Denis
AU - Haegeman, Guy
PY - 2011/9/1
Y1 - 2011/9/1
N2 - We have analyzed in molecular detail how kurarinone, a lavandulyl flavanone isolated from Sophora flavescens, suppresses nuclear factor-κB (NFκB)-driven interleukin-6 (IL6) expression and cancer cell growth. Interleukin-6 (IL6), involved in cancer-related inflammation, acts as an autocrine and paracrine growth factor, which promotes angiogenesis, metastasis, and subversion of immunity, and changes responsivity to hormones and to chemotherapeutics. Our results in estrogen-unresponsive fibroblasts, ribosomal S6 kinase 2 kinase (RSK2) knockout cells, and estrogen receptor (ER)-deficient breast tumor cells show that kurarinone can inhibit tumor cell proliferation and selectively block nuclear NFκB transactivation of specific target genes such as IL6, cyclin D1, SOD2 but not TNFAIP2. This occurs via attenuation of extracellular signal-regulated protein (ERK) and RSK2 kinase pathways and inhibition of S6 kinase ribosomal protein (S6RP) and histone H3 S10 phosphorylation. As constitutive NFκB and RSK2 activity are important hallmarks of human cancers, including hematopoietic malignancies and solid tumors, prenylated flavanones represent an attractive class of natural inhibitors of the ERK/RSK2 signaling pathway for cancer therapy.
AB - We have analyzed in molecular detail how kurarinone, a lavandulyl flavanone isolated from Sophora flavescens, suppresses nuclear factor-κB (NFκB)-driven interleukin-6 (IL6) expression and cancer cell growth. Interleukin-6 (IL6), involved in cancer-related inflammation, acts as an autocrine and paracrine growth factor, which promotes angiogenesis, metastasis, and subversion of immunity, and changes responsivity to hormones and to chemotherapeutics. Our results in estrogen-unresponsive fibroblasts, ribosomal S6 kinase 2 kinase (RSK2) knockout cells, and estrogen receptor (ER)-deficient breast tumor cells show that kurarinone can inhibit tumor cell proliferation and selectively block nuclear NFκB transactivation of specific target genes such as IL6, cyclin D1, SOD2 but not TNFAIP2. This occurs via attenuation of extracellular signal-regulated protein (ERK) and RSK2 kinase pathways and inhibition of S6 kinase ribosomal protein (S6RP) and histone H3 S10 phosphorylation. As constitutive NFκB and RSK2 activity are important hallmarks of human cancers, including hematopoietic malignancies and solid tumors, prenylated flavanones represent an attractive class of natural inhibitors of the ERK/RSK2 signaling pathway for cancer therapy.
KW - Animals
KW - Breast Neoplasms
KW - Cell Line
KW - Cell Line, Tumor
KW - Cell Proliferation
KW - Extracellular Signal-Regulated MAP Kinases
KW - Female
KW - Flavanones
KW - Flavonoids
KW - Gene Expression Regulation, Enzymologic
KW - Humans
KW - MAP Kinase Signaling System
KW - Mice
KW - Plant Extracts
KW - Plant Roots
KW - Protein-Serine-Threonine Kinases
KW - Ribosomal Protein S6 Kinases, 90-kDa
KW - Sophora
M3 - SCORING: Journal article
C2 - 21831037
VL - 11
SP - 247
EP - 261
JO - ENDOCR METAB IMMUNE
JF - ENDOCR METAB IMMUNE
SN - 1871-5303
IS - 3
ER -