Abstract
The focus of this study was to develop additive or synergistic agents to chemosensitize the existing chemotherapeutic drug in human non – small cell lung cancer (NSCLC). In this study employing analyses of the NF-κB/ I-κB kinase (IKK) signal cascade in a number of NSCLC cell lines, we report the identification and characterization of parthenolide. Parthenolide is a sesquiterpene lactone that can antagonize paclitaxel-mediated NF-κB nuclear translocation and activation through selectively targeting I-κB kinase (IKK) activity. Our results showed that parthenolide dramatically lowered the effective dose of Paclitaxel needed to induce cytotoxicity of a wide range of NSCLC cell lines. An examination of pathways common to Paclitaxel and parthenolide signaling revealed that this synergy was related to modulation of the NF-κB/ I-κB kinase (IKK) signal cascade through IKKß. Parthenolide alone induced apoptosis via the mitochondria/ caspase pathway. Moreover, in a human orthotopic NSCLC xenograft model, a well-tolerated combination induces tumor regression. These data strengthen the rationale for the use of parthenolide to decrease the apoptotic threshold via a caspase-dependent process and support the use of concurrent low doses of paclitaxel in the treatment of NSCLC with paclitaxel chemoresistance.
Keywords: Synergy, IKK, NF-κB, caspase dependent.
Current Cancer Drug Targets
Title:Paclitaxel Efficacy is Increased by Parthenolide via Nuclear Factor- KappaB Pathways in In Vitro and In Vivo Human Non–Small Cell Lung Cancer Models
Volume: 10 Issue: 7
Author(s): Z. W. Gao, D. L. Zhang and C. B. Guo
Affiliation:
Keywords: Synergy, IKK, NF-κB, caspase dependent.
Abstract: The focus of this study was to develop additive or synergistic agents to chemosensitize the existing chemotherapeutic drug in human non – small cell lung cancer (NSCLC). In this study employing analyses of the NF-κB/ I-κB kinase (IKK) signal cascade in a number of NSCLC cell lines, we report the identification and characterization of parthenolide. Parthenolide is a sesquiterpene lactone that can antagonize paclitaxel-mediated NF-κB nuclear translocation and activation through selectively targeting I-κB kinase (IKK) activity. Our results showed that parthenolide dramatically lowered the effective dose of Paclitaxel needed to induce cytotoxicity of a wide range of NSCLC cell lines. An examination of pathways common to Paclitaxel and parthenolide signaling revealed that this synergy was related to modulation of the NF-κB/ I-κB kinase (IKK) signal cascade through IKKß. Parthenolide alone induced apoptosis via the mitochondria/ caspase pathway. Moreover, in a human orthotopic NSCLC xenograft model, a well-tolerated combination induces tumor regression. These data strengthen the rationale for the use of parthenolide to decrease the apoptotic threshold via a caspase-dependent process and support the use of concurrent low doses of paclitaxel in the treatment of NSCLC with paclitaxel chemoresistance.
Export Options
About this article
Cite this article as:
W. Gao Z., L. Zhang D. and B. Guo C., Paclitaxel Efficacy is Increased by Parthenolide via Nuclear Factor- KappaB Pathways in In Vitro and In Vivo Human Non–Small Cell Lung Cancer Models, Current Cancer Drug Targets 2010; 10 (7) . https://dx.doi.org/10.2174/156800910793605776
DOI https://dx.doi.org/10.2174/156800910793605776 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- 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
Related Articles
-
Cyanidin 3-O-Glucoside Induces the Apoptosis in the Osteosarcoma Cells through Upregulation of the PPARγ and P21: An <i>In Vitro</i> Study
Anti-Cancer Agents in Medicinal Chemistry The Parathyroid Hormone Receptorsome and the Potential for Therapeutic Intervention
Current Drug Targets Emerging Features in the Regulation of MMP-9 Gene Expression for the Development of Novel Molecular Targets and Therapeutic Strategies
Current Drug Targets - Inflammation & Allergy Vitamin D Represses the Aggressive Potential of Osteosarcoma
Endocrine, Metabolic & Immune Disorders - Drug Targets EXTraordinary Bones: Functional and Genetic Analysis of the EXT Gene Family
Current Genomics Novel Targets for Apoptosis Modulation: BAG3 Protein and Other Co- Chaperones
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Deciphering the Role of Forkhead Transcription Factors in Cancer Therapy
Current Drug Targets In Vitro Inhibitory Effect of Recombinant Human Calprotectin on Nalm6 Leukemia Cell Line
Anti-Cancer Agents in Medicinal Chemistry Anti-VEGF Mediated Immunomodulatory Role of Phytochemicals: Scientific Exposition for Plausible HCC Treatment
Current Drug Targets FAK and p53 Protein Interactions
Anti-Cancer Agents in Medicinal Chemistry Angiogenesis: A Target for Cancer Therapy
Current Pharmaceutical Design Promises and Challenges of Adult Stem Cells in Cancer Therapy
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Electrochemical Cell-based Biosensors for Biomedical Applications
Current Topics in Medicinal Chemistry Activation of CAR and PXR by Dietary, Environmental and Occupational Chemicals Alters Drug Metabolism, Intermediary Metabolism, and Cell Proliferation
Current Pharmacogenomics and Personalized Medicine Nanotechnology and Animal Health
Pharmaceutical Nanotechnology LncRNAs as Architects in Cancer Biomarkers with Interface of Epitranscriptomics- Incipient Targets in Cancer Therapy
Current Cancer Drug Targets Clinical Pharmacogenetics of Methotrexate
Current Drug Metabolism Targeted Delivery of Anti-Inflammatory Agents to Tumors
Current Pharmaceutical Design Advancement of Targeted Ultrasound Contrast Agents and their Applications in Molecular Imaging and Targeted Therapy
Current Pharmaceutical Design CXCR4 Inhibitors: Tumor Vasculature and Therapeutic Challenges
Recent Patents on Anti-Cancer Drug Discovery