Abstract
Curcumin, a major component of the golden spice turmeric (Curcuma longa), has been linked with the prevention and treatment of a wide variety of cancers through modulation of multiple cell signaling pathways. Since the first report from our laboratory in 1995 that curcumin can inhibit activation of the proinflammatory transcription factor NF-κB by inhibiting the 26S proteasomal degradation of IκBα, an inhibitor of NF-κB, this yellow pigment has been shown to inhibit the protease activities of the proteasome. The carbonyl carbons of the curcumin molecule directly interact with the hydroxyl group of the amino-terminal threonine residue of the proteasomal CT-L subunit of 20S proteasome and cellular 26S proteasome. Curcumin is also a potent inhibitor of COP9 signalosome and associated kinases, casein kinase 2 and protein kinase D, all linked to the ubiquitin-proteasomal system (UPS). Curcumin can also directly inhibit ubiquitin isopeptidases, a family of deubiquitinases (DUBs) that salvage ubiquitin for reuse by the 26S proteasome system. The inhibition of this enzyme by curcumin is mediated through α,β-unsaturated ketone and two sterically accessible β-carbons. Regulation of the UPS pathway by curcumin has been linked to regulation of cancer-linked inflammatory proteins (such as COX-2 and iNOS), transcription factors (NF-κB, STAT3, Sp, AP-1, GADD153/CHOP, HIF-1α), growth factors (VEGF, HER2), apoptotic proteins (p53, Bcl-2, survivin, DNA topoisomerase II, HDAC2, p300, hTERT) and cell cycle proteins (cyclin D1, cyclin E, cyclin B, p21, p27) associated with the prevention and therapy of cancer. Interestingly, the effect of curcumin on 26S proteasome appears to be dose-dependent, as low doses (≥1 µM) increase proteasome activity whereas high doses (≤10 µM) inhibit the proteasome activity. In this review, we discuss in detail how modulation of these targets by curcumin is linked to prevention and treatment of cancer.
Keywords: Cancer, cell death, curcumin, degradation, inflammatory protein, prevention, proteasome, transcription factor, treatment, ubiquitination.
Current Medicinal Chemistry
Title:Targeting Proteasomal Pathways by Dietary Curcumin for Cancer Prevention and Treatment
Volume: 21 Issue: 14
Author(s): Noor Hasima and Bharat B. Aggarwal
Affiliation:
Keywords: Cancer, cell death, curcumin, degradation, inflammatory protein, prevention, proteasome, transcription factor, treatment, ubiquitination.
Abstract: Curcumin, a major component of the golden spice turmeric (Curcuma longa), has been linked with the prevention and treatment of a wide variety of cancers through modulation of multiple cell signaling pathways. Since the first report from our laboratory in 1995 that curcumin can inhibit activation of the proinflammatory transcription factor NF-κB by inhibiting the 26S proteasomal degradation of IκBα, an inhibitor of NF-κB, this yellow pigment has been shown to inhibit the protease activities of the proteasome. The carbonyl carbons of the curcumin molecule directly interact with the hydroxyl group of the amino-terminal threonine residue of the proteasomal CT-L subunit of 20S proteasome and cellular 26S proteasome. Curcumin is also a potent inhibitor of COP9 signalosome and associated kinases, casein kinase 2 and protein kinase D, all linked to the ubiquitin-proteasomal system (UPS). Curcumin can also directly inhibit ubiquitin isopeptidases, a family of deubiquitinases (DUBs) that salvage ubiquitin for reuse by the 26S proteasome system. The inhibition of this enzyme by curcumin is mediated through α,β-unsaturated ketone and two sterically accessible β-carbons. Regulation of the UPS pathway by curcumin has been linked to regulation of cancer-linked inflammatory proteins (such as COX-2 and iNOS), transcription factors (NF-κB, STAT3, Sp, AP-1, GADD153/CHOP, HIF-1α), growth factors (VEGF, HER2), apoptotic proteins (p53, Bcl-2, survivin, DNA topoisomerase II, HDAC2, p300, hTERT) and cell cycle proteins (cyclin D1, cyclin E, cyclin B, p21, p27) associated with the prevention and therapy of cancer. Interestingly, the effect of curcumin on 26S proteasome appears to be dose-dependent, as low doses (≥1 µM) increase proteasome activity whereas high doses (≤10 µM) inhibit the proteasome activity. In this review, we discuss in detail how modulation of these targets by curcumin is linked to prevention and treatment of cancer.
Export Options
About this article
Cite this article as:
Hasima Noor and Aggarwal B. Bharat, Targeting Proteasomal Pathways by Dietary Curcumin for Cancer Prevention and Treatment, Current Medicinal Chemistry 2014; 21 (14) . https://dx.doi.org/10.2174/09298673113206660135
DOI https://dx.doi.org/10.2174/09298673113206660135 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
- Announcements
Related Articles
-
Synthesis and Evaluation of Novel Erucin Analogues as Potential Antitumor Compounds
Letters in Organic Chemistry Pharmacogenetics, Pharmacogenomics and Epigenetics of Nrf2-regulated Xenobioticmetabolizing Enzymes and Transporters by Dietary Phytochemical and Cancer Chemoprevention
Current Drug Metabolism The Functions of Heparanase in Human Diseases
Mini-Reviews in Medicinal Chemistry Antioxidant Properties and Medicinal Uses of Some Crataegus Spp. (Hawthorn) Including <i>C. meyeri</i> and <i>C. pontica</i>
Current Nutrition & Food Science MiR-125b Inhibits Cell Proliferation and Induces Apoptosis in Human Colon Cancer SW480 Cells <i>via</i> Targeting STAT3
Recent Patents on Anti-Cancer Drug Discovery Molecular Mechanisms of Anti-cancer Action of Garlic Compounds in Neuroblastoma
Anti-Cancer Agents in Medicinal Chemistry The Prognostic Value of Cytokeratin and Extracellular Collagen Expression in Urinary Bladder Cancer
Current Molecular Medicine Alkaloids and Flavonoids as α1-Adrenergic Receptor Antagonists
Current Medicinal Chemistry Computational Approaches for the Identification and Optimization of Src Family Kinases Inhibitors
Current Medicinal Chemistry Tyrosine Kinase Inhibitor-Induced Hypertension: Role of Hypertension as a Biomarker in Cancer Treatment
Current Vascular Pharmacology Fc-fusion Proteins in Therapy: An Updated View
Current Medicinal Chemistry Short-Term Intra-Nasal Erythropoietin Administration with Low Sialic Acid Content is without Toxicity or Erythropoietic Effects
Current Neurovascular Research Non Smoking for Successful Aging: Therapeutic Perspectives
Current Pharmaceutical Design Editorial ( Thematic Issue: Diabetes and Cancer - Disease, Drugs or Deception?)
Current Drug Safety Pharmacological Targets for the Inhibition of Neurogenic Inflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Adrenomedullin: A Tumor Progression Factor via Angiogenic Control
Current Cancer Drug Targets G4 Aptamers: Trends in Structural Design
Mini-Reviews in Medicinal Chemistry In Situ Gene Therapy for Prostate Cancer
Current Gene Therapy Killer Beacons for Combined Cancer Imaging and Therapy
Current Medicinal Chemistry Druggability of Mortalin for Cancer and Neuro-Degenerative Disorders
Current Pharmaceutical Design