Abstract
Melatonin, as a new member of an expanding group of regulatory factors that control cell proliferation and loss, is the only known chronobiotic, hormonal regulator of neoplastic cell growth. At physiological circulating concentrations, this indoleamine is cytostatic and inhibits cancer cell proliferation in vitro via specific cell cycle effects. At pharmacological concentrations, melatonin exhibits cytotoxic activity in cancer cells. At both physiological and pharmacological concentrations, melatonin acts as a differentiating agent in some cancer cells and lowers their invasive and metastatic status through alterations in adhesion molecules and maintenance of gap junctional intercellular communication. In other cancer cell types, melatonin, either alone or in combination with other agents, induces apoptotic cell death. Biochemical and molecular mechanisms of melatonins oncostatic action may include regulation of estrogen receptor expression and transactivation, calcium / calmodulin activity, prote in kinase C activity, cytoskeletal architecture and function, intracellular redox status, melatonin receptor-mediated signal transduction cascades, and fatty acid transport and metabolism. A major mechanism mediating melatonins circadian stage-dependent tumor growth inhibitory action is the suppression of epidermal growth factor receptor (EGFR) / mitogen-activated protein kinase (MAPK) activity. This occurs via melatonin receptor-mediated blockade of tumor linoleic acid uptake and its conversion to 13-hydroxyoctadecadienoic acid (13-HODE) which normally activates EGFR / MAPK mitogenic signaling. This represents a potentially unifying model for the chronobiological inhibitory regulation of cancer growth by melatonin in the maintenance of the host / cancer balance. It also provides the first biological explanation of melatonin-induced enhancement of the efficacy and reduced toxicity of chemo- and radiotherapy in cancer patients.
Keywords: Circadian-Based Cancer Therapy, 13-hydroxyoctadecadienoic acid (13-HODE), Estrogen Response Pathway, glutathione (GSH), Chronobiological
Current Topics in Medicinal Chemistry
Title: Melatonin as a Chronobiotic / Anticancer Agent: Cellular, Biochemical, and Molecular Mechanisms of Action and their Implications for Circadian-Based Cancer Therapy
Volume: 2 Issue: 2
Author(s): David E. Blask, Leonard A. Sauer and Robert T. Dauchy
Affiliation:
Keywords: Circadian-Based Cancer Therapy, 13-hydroxyoctadecadienoic acid (13-HODE), Estrogen Response Pathway, glutathione (GSH), Chronobiological
Abstract: Melatonin, as a new member of an expanding group of regulatory factors that control cell proliferation and loss, is the only known chronobiotic, hormonal regulator of neoplastic cell growth. At physiological circulating concentrations, this indoleamine is cytostatic and inhibits cancer cell proliferation in vitro via specific cell cycle effects. At pharmacological concentrations, melatonin exhibits cytotoxic activity in cancer cells. At both physiological and pharmacological concentrations, melatonin acts as a differentiating agent in some cancer cells and lowers their invasive and metastatic status through alterations in adhesion molecules and maintenance of gap junctional intercellular communication. In other cancer cell types, melatonin, either alone or in combination with other agents, induces apoptotic cell death. Biochemical and molecular mechanisms of melatonins oncostatic action may include regulation of estrogen receptor expression and transactivation, calcium / calmodulin activity, prote in kinase C activity, cytoskeletal architecture and function, intracellular redox status, melatonin receptor-mediated signal transduction cascades, and fatty acid transport and metabolism. A major mechanism mediating melatonins circadian stage-dependent tumor growth inhibitory action is the suppression of epidermal growth factor receptor (EGFR) / mitogen-activated protein kinase (MAPK) activity. This occurs via melatonin receptor-mediated blockade of tumor linoleic acid uptake and its conversion to 13-hydroxyoctadecadienoic acid (13-HODE) which normally activates EGFR / MAPK mitogenic signaling. This represents a potentially unifying model for the chronobiological inhibitory regulation of cancer growth by melatonin in the maintenance of the host / cancer balance. It also provides the first biological explanation of melatonin-induced enhancement of the efficacy and reduced toxicity of chemo- and radiotherapy in cancer patients.
Export Options
About this article
Cite this article as:
Blask E. David, Sauer A. Leonard and Dauchy T. Robert, Melatonin as a Chronobiotic / Anticancer Agent: Cellular, Biochemical, and Molecular Mechanisms of Action and their Implications for Circadian-Based Cancer Therapy, Current Topics in Medicinal Chemistry 2002; 2 (2) . https://dx.doi.org/10.2174/1568026023394407
DOI https://dx.doi.org/10.2174/1568026023394407 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Aldehyde Dehydrogenase as a Marker for Stem Cells
Current Stem Cell Research & Therapy Insulin-like Growth Factor I Receptor: A Novel Target for Hepatocellular Carcinoma Gene Therapy
Mini-Reviews in Medicinal Chemistry Pharmacogenomics
Current Drug Metabolism Tumor Systems Need to be Rendered Usable for a New Action-Theoretical Abstraction: The Starting Point for Novel Therapeutic Options
Current Cancer Therapy Reviews Enhanced Oral Bioavailability of The Hydrophobic Chemopreventive Agent (Sr13668) in Beagle Dogs
Current Pharmaceutical Biotechnology Molecular Targets, Anti-cancer Properties and Potency of Synthetic Indole-3-carbinol Derivatives
Mini-Reviews in Medicinal Chemistry Exploiting HPV-Induced Carcinogenesis for a Rational Drug Development in Cervical Cancer
Current Cancer Drug Targets Novel Agents in the Management of Lung Cancer
Current Medicinal Chemistry Procyanidin B2 3,3″-di-O-gallate Inhibits Endothelial Cells Growth and Motility by Targeting VEGFR2 and Integrin Signaling Pathways
Current Cancer Drug Targets Dysregulated Chemokine Signaling in Cystic Fibrosis Lung Disease: A Potential Therapeutic Target
Current Drug Targets Perspectives on Medicinal Properties of Mangiferin
Mini-Reviews in Medicinal Chemistry Evaluation of Salivary Melatonin Levels in HIV-positive Patients: A Historical Cohort Study
Reviews on Recent Clinical Trials Pulmonary Hypertension and Systemic Diseases
Current Drug Targets - Inflammation & Allergy AGE-RAGE System and Carcinogenesis
Current Pharmaceutical Design GPER Overexpression in Cervical Cancer Versus Premalignant Lesions: Its Activation Induces Different Forms of Cell Death
Anti-Cancer Agents in Medicinal Chemistry In Vitro and In Vivo Evaluation of DMSO and Azone as Penetration Enhancers for Cutaneous Application of Celecoxib
Current Drug Delivery Fluorinated Natural Products with Clinical Significance
Current Topics in Medicinal Chemistry Diabetes, Cancer and Treatment – A Mini-Review
Current Drug Safety Effects of Intermittent Hypoxia on Expression of Glucose Metabolism Genes in MCF7 Breast Cancer Cell Line
Current Cancer Drug Targets Breast Cancer Detection and Classification using Traditional Computer Vision Techniques: A Comprehensive Review
Current Medical Imaging