Abstract
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.
Keywords: NFkappaB, kinase, inflammation, RSK2, ERK, Vasculature, cancer, histone H3, Sophora flavescens, Interleukin-6, post-menopausal, osteoporosis, endometrium, prostate
Endocrine, Metabolic & Immune Disorders - Drug Targets
Title: Attenuation of ERK/RSK2-Driven NFκB Gene Expression and Cancer Cell Proliferation by Kurarinone, a Lavandulyl Flavanone Isolated from Sophora flavescens Ait. Roots
Volume: 11 Issue: 3
Author(s): Wim Vanden Berghe, An De Naeyer, Nathalie Dijsselbloem, Jean-Pierre David, Denis De Keukeleire and Guy Haegeman
Affiliation:
Keywords: NFkappaB, kinase, inflammation, RSK2, ERK, Vasculature, cancer, histone H3, Sophora flavescens, Interleukin-6, post-menopausal, osteoporosis, endometrium, prostate
Abstract: 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.
Export Options
About this article
Cite this article as:
Vanden Berghe Wim, De Naeyer An, Dijsselbloem Nathalie, David Jean-Pierre, De Keukeleire Denis and Haegeman Guy, Attenuation of ERK/RSK2-Driven NFκB Gene Expression and Cancer Cell Proliferation by Kurarinone, a Lavandulyl Flavanone Isolated from Sophora flavescens Ait. Roots, Endocrine, Metabolic & Immune Disorders - Drug Targets 2011; 11 (3) . https://dx.doi.org/10.2174/187153011796429790
DOI https://dx.doi.org/10.2174/187153011796429790 |
Print ISSN 1871-5303 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3873 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Prediction of Disease-Related Genes Based on Hybrid Features
Current Proteomics Cancer and Treatment Modalities
Current Cancer Therapy Reviews Co-opting Functions of Cholinesterases in Neural, Limb and Stem Cell Development
Protein & Peptide Letters Pharmacologic Evidence of Green Tea in Targeting Tyrosine Kinases
Current Reviews in Clinical and Experimental Pharmacology Withdrawal Notice: Role, Significance and Association of microRNA-10a/b in Physiology of Cancer
MicroRNA Osteoblast Differentiation and Control by Vitamin D and Vitamin D Metabolites
Current Pharmaceutical Design Pharmacological and Biological Therapies for Metabolic Bone Disease in Critical Illness: An Integrative Physiology Approach
Current Drug Therapy Screening and Interaction Analysis of Key Genes in miR-542-3p Over- Expressed Osteosarcoma Cells by Bioinformatics
Combinatorial Chemistry & High Throughput Screening E2F1 and NF-κB: Key Mediators of Inflammation-associated Cancers and Potential Therapeutic Targets
Current Cancer Drug Targets Src Kinase Inhibitors: An Update on Patented Compounds
Current Medicinal Chemistry Micro-/Nano-Scale Biointerfaces, Mechanical Coupling and Cancer Therapy
Current Topics in Medicinal Chemistry Marine Derived Anticancer Drugs Targeting Microtubule
Recent Patents on Anti-Cancer Drug Discovery Identification of AHSA1 as a Potential Therapeutic Target for Breast Cancer: Bioinformatics Analysis and <i>in vitro</i> Studies
Current Cancer Drug Targets Melittin: A Natural Peptide with Expanded Therapeutic Applications
The Natural Products Journal Potential Therapeutic Targets of Curcumin, Most Abundant Active Compound of Turmeric Spice: Role in the Management of Various Types of Cancer
Recent Patents on Anti-Cancer Drug Discovery Anabolics in Osteoporosis: The Emerging Therapeutic Tool
Current Molecular Medicine Applications of Nanosystems to Anticancer Drug Therapy (Part II. Dendrimers, Micelles, Lipid-based Nanosystems)
Recent Patents on Anti-Cancer Drug Discovery Post-menopausal Osteoporosis and Probiotics
Current Drug Targets Investigation of Gene Expression Pattern of 5HTR2a and MAO-A in PBMCs of Individuals Who Had Been Exposed to Air Pollution in Highly Polluted Area
Recent Patents on Inflammation & Allergy Drug Discovery 15,16-dihydrotanshinone I Induces Apoptosis and Inhibits the Proliferation, Migration of Human Osteosarcoma Cell Line 143B in vitro
Anti-Cancer Agents in Medicinal Chemistry