Abstract
Melatonin exerts oncostatic effects on different kinds of tumors, especially on hormone-dependent breast cancer. The general conclusion is that melatonin, in vivo, reduces the incidence and growth of chemically-induced mammary tumors in rodents, and, in vitro, inhibits the proliferation and invasiveness of human breast cancer cells. Both studies support the hypothesis that melatonin inhibits the growth of breast cancer by interacting with estrogen-signaling pathways through three different mechanisms: (a) the indirect neuroendocrine mechanism which includes the melatonin downregulation of the hypothalamic-pituitary-reproductive axis and the consequent reduction of circulating levels of gonadal estrogens, (b) direct melatonin actions at tumor cell level by interacting with the activation of the estrogen receptor, thus behaving as a selective estrogen receptor modulator (SERM), and (c) the regulation of the enzymes involved in the biosynthesis of estrogens in peripheral tissues, thus behaving as a selective estrogen enzyme modulator (SEEM). As melatonin reduces the activity and expression of aromatase, sulfatase and 17β-hydroxysteroid dehydrogenase and increases the activity and expression of estrogen sulfotransferase, it may protect mammary tissue from excessive estrogenic effects. Thus, a single molecule has both SERM and SEEM properties, one of the main objectives desired for the breast antitumoral drugs. Since the inhibition of enzymes involved in the biosynthesis of estrogens is currently one of the first therapeutic strategies used against the growth of breast cancer, melatonin modulation of different enzymes involved in the synthesis of steroid hormones makes, collectively, this indolamine an interesting anticancer drug in the prevention and treatment of estrogen-dependent mammary tumors.
Keywords: Melatonin, pineal gland, breast cancer, estradiol, aromatase, sulfatase, sulfotransferase, 17β-hydroxysteroid dehydrogenase
Current Cancer Drug Targets
Title: Melatonin as a Selective Estrogen Enzyme Modulator
Volume: 8 Issue: 8
Author(s): S. Cos, A. Gonzalez, C. Martinez-Campa, M. D. Mediavilla, C. Alonso-Gonzalez and E. J. Sanchez-Barcelo
Affiliation:
Keywords: Melatonin, pineal gland, breast cancer, estradiol, aromatase, sulfatase, sulfotransferase, 17β-hydroxysteroid dehydrogenase
Abstract: Melatonin exerts oncostatic effects on different kinds of tumors, especially on hormone-dependent breast cancer. The general conclusion is that melatonin, in vivo, reduces the incidence and growth of chemically-induced mammary tumors in rodents, and, in vitro, inhibits the proliferation and invasiveness of human breast cancer cells. Both studies support the hypothesis that melatonin inhibits the growth of breast cancer by interacting with estrogen-signaling pathways through three different mechanisms: (a) the indirect neuroendocrine mechanism which includes the melatonin downregulation of the hypothalamic-pituitary-reproductive axis and the consequent reduction of circulating levels of gonadal estrogens, (b) direct melatonin actions at tumor cell level by interacting with the activation of the estrogen receptor, thus behaving as a selective estrogen receptor modulator (SERM), and (c) the regulation of the enzymes involved in the biosynthesis of estrogens in peripheral tissues, thus behaving as a selective estrogen enzyme modulator (SEEM). As melatonin reduces the activity and expression of aromatase, sulfatase and 17β-hydroxysteroid dehydrogenase and increases the activity and expression of estrogen sulfotransferase, it may protect mammary tissue from excessive estrogenic effects. Thus, a single molecule has both SERM and SEEM properties, one of the main objectives desired for the breast antitumoral drugs. Since the inhibition of enzymes involved in the biosynthesis of estrogens is currently one of the first therapeutic strategies used against the growth of breast cancer, melatonin modulation of different enzymes involved in the synthesis of steroid hormones makes, collectively, this indolamine an interesting anticancer drug in the prevention and treatment of estrogen-dependent mammary tumors.
Export Options
About this article
Cite this article as:
Cos S., Gonzalez A., Martinez-Campa C., Mediavilla D. M., Alonso-Gonzalez C. and Sanchez-Barcelo J. E., Melatonin as a Selective Estrogen Enzyme Modulator, Current Cancer Drug Targets 2008; 8 (8) . https://dx.doi.org/10.2174/156800908786733469
DOI https://dx.doi.org/10.2174/156800908786733469 |
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
-
Targeted Nanosystems for Cancer Therapy
Current Cancer Therapy Reviews The Role of a Human Hematopoietic Mesenchymal Progenitor in Wound Healing and Fibrotic Diseases and Implications for Therapy
Current Stem Cell Research & Therapy Restoring p53 Function in Cancer: Novel Therapeutic Approaches for Applying the Brakes to Tumorigenesis
Recent Patents on Anti-Cancer Drug Discovery HPC Analysis of Multiple Binding Sites Communication and Allosteric Modulations in Drug Design: The HSP Case Study
Current Drug Targets Walking a Tightrope: A Perspective of Resveratrol Effects on Breast Cancer
Current Protein & Peptide Science HIV-1 Tat Disrupts CX3CL1-CX3CR1 Axis in Microglia via the NF-κBYY1 Pathway
Current HIV Research MicroRNAs Patents: The Road From Bench to Bedsides for Cancer Treatment
Recent Patents on DNA & Gene Sequences Emerging Treatments in Acute Lymphoblastic Leukemia
Current Cancer Drug Targets Bcl-2 Family Proteins as Therapeutic Targets
Current Pharmaceutical Design Targeting Cytotoxic Conjugates of Somatostatin, Luteinizing Hormone- Releasing Hormone and Bombesin to Cancers Expressing Their Receptors: A “Smarter” Chemotherapy
Current Pharmaceutical Design Hereditary Breast Cancer in Sub-Saharan Africa
Current Women`s Health Reviews Nitric Oxide Releasing Nanomaterials for Cancer Treatment: Current Status and Perspectives
Current Topics in Medicinal Chemistry B Cell Responses to Oxidative Stress
Current Pharmaceutical Design Targeting Tumour Metastasis: The Emerging Role of Nanotechnology
Current Medicinal Chemistry Tyrosine Kinase Blockers: New Hope for Successful Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Mixed Connective Tissue Disease (MCTD) – A Coming of Age
Current Rheumatology Reviews STAT3 as a Therapeutic Target for Glioblastoma
Anti-Cancer Agents in Medicinal Chemistry Biomimetic Approaches Towards The Synthesis of Complex Dimeric Natural Products
Current Pharmaceutical Design Possibilities of Poly(D,L-lactide-co-glycolide) in the Formulation of Nanomedicines Against Cancer
Current Drug Targets Role of Topological, Electronic, Geometrical, Constitutional and Quantum Chemical Based Descriptors in QSAR: mPGES-1 as a Case Study
Current Topics in Medicinal Chemistry