Abstract
Endogenous estrogens, such as 17β-estradiol (E2), are implicated in the development of breast cancer. The putative mechanisms by which estrogens exert the carcinogenic effects have been recognized to involve the redox cycling of estrogen metabolites and subsequent estrogen-DNA adduct formation as well as the estrogen receptor-dependent pathway of estrogen-induced cell growth. The former pathway is regulated by phase I enzymes, mainly cytochrome P450 (CYP) 1A1, 1A2, and 1B1. Among them, CYP1B1 predominantly catalyzes the C4-position of E2 and forms carcinogenic 4-hydroxy-E2 (4-OHE2), whereas CYP1A1 and CYP1A2 convert E2 to noncarcinogenic 2-hydroxy-E2. Formed 4-OHE2 is further oxidized to semiquinones and quinones, which form DNA adducts, leading to mutagenic lesions. Consequently, CYP1B1 is highly expressed, and 4-OHE2 is predominantly detected in estrogen target neoplastic tissues. Moreover, invasion and metastasis are also involved in the development of breast cancer. Epidemiological studies suggest an inverse association between a higher intake of flavonoids and breast cancer risk. Flavonoids, which are widely distributed in the plant kingdom, have been recently reported as candidate compounds that can exert chemopreventive effects in estrogen-dependent or independent breast cancer. In this review, we provide a comprehensive overview of breast cancer and chemoprevention by flavonoids, mainly focusing on ER-mediated hormonal regulation, redox cycling of estrogen metabolites, and selective inhibition of CYP1B1.
Keywords: Estrogen, breast cancer, CYP1B1, chemoprevention, flavonoids.
Current Pharmaceutical Design
Title:Breast Cancer and Flavonoids - A Role in Prevention
Volume: 19 Issue: 34
Author(s): Hitomi Takemura, Hiroyuki Sakakibara, Shunsuke Yamazaki and Kayoko Shimoi
Affiliation:
Keywords: Estrogen, breast cancer, CYP1B1, chemoprevention, flavonoids.
Abstract: Endogenous estrogens, such as 17β-estradiol (E2), are implicated in the development of breast cancer. The putative mechanisms by which estrogens exert the carcinogenic effects have been recognized to involve the redox cycling of estrogen metabolites and subsequent estrogen-DNA adduct formation as well as the estrogen receptor-dependent pathway of estrogen-induced cell growth. The former pathway is regulated by phase I enzymes, mainly cytochrome P450 (CYP) 1A1, 1A2, and 1B1. Among them, CYP1B1 predominantly catalyzes the C4-position of E2 and forms carcinogenic 4-hydroxy-E2 (4-OHE2), whereas CYP1A1 and CYP1A2 convert E2 to noncarcinogenic 2-hydroxy-E2. Formed 4-OHE2 is further oxidized to semiquinones and quinones, which form DNA adducts, leading to mutagenic lesions. Consequently, CYP1B1 is highly expressed, and 4-OHE2 is predominantly detected in estrogen target neoplastic tissues. Moreover, invasion and metastasis are also involved in the development of breast cancer. Epidemiological studies suggest an inverse association between a higher intake of flavonoids and breast cancer risk. Flavonoids, which are widely distributed in the plant kingdom, have been recently reported as candidate compounds that can exert chemopreventive effects in estrogen-dependent or independent breast cancer. In this review, we provide a comprehensive overview of breast cancer and chemoprevention by flavonoids, mainly focusing on ER-mediated hormonal regulation, redox cycling of estrogen metabolites, and selective inhibition of CYP1B1.
Export Options
About this article
Cite this article as:
Takemura Hitomi, Sakakibara Hiroyuki, Yamazaki Shunsuke and Shimoi Kayoko, Breast Cancer and Flavonoids - A Role in Prevention, Current Pharmaceutical Design 2013; 19 (34) . https://dx.doi.org/10.2174/1381612811319340006
DOI https://dx.doi.org/10.2174/1381612811319340006 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Editorial (Thematic Issue: Targeting Transporters for CNS Drug Delivery)
Current Pharmaceutical Design Medicinal Chemistry of Hsp90 Inhibitors
Current Topics in Medicinal Chemistry Intracellular Delivery of Potential Therapeutic Genes: Prospects in Cancer Gene Therapy
Current Gene Therapy Changes in the Expression of the Alzheimers Disease-Associated Presenilin Gene in Drosophila Heart Leads to Cardiac Dysfunction
Current Alzheimer Research Novel Small-Molecule Inhibitors of Arylamine N-Acetyltransferases: Drug Discovery by High Throughput Screening
Combinatorial Chemistry & High Throughput Screening Current Trends in the Application of Nanoparticles in Drug Delivery
Current Medicinal Chemistry Key Sites for P2X Receptor Function and Multimerization: Overview of Mutagenesis Studies on a Structural Basis
Current Medicinal Chemistry Biologic Therapy in Immune Mediated Inflammatory Disease: Basic Science and Clinical Concepts
Current Drug Safety Nanotechnologies: A Strategy to Overcome Blood-Brain Barrier
Current Drug Metabolism The Functions of F-box Proteins in Regulating the Epithelial to Mesenchymal Transition
Current Pharmaceutical Design β-sitosterol: Bioactive Compounds in Foods, their Role in Health Promotion and Disease Prevention “A Concise Report of its Phytopharmaceutical Importance”
Current Traditional Medicine Failure of Immune Homeostasis - The Consequences of Under and Over Reactivity
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Current Molecularly Targeting Therapies in NSCLC and Melanoma
Anti-Cancer Agents in Medicinal Chemistry Small-Molecule Inhibitors of Bcl-2 Family Proteins as Therapeutic Agents in Cancer
Recent Patents on Anti-Cancer Drug Discovery Consumption of Cooked Navy Bean Powders Modulate the Canine Fecal and Urine Metabolome
Current Metabolomics Targeting Aldose Reductase for the Treatment of Cancer
Current Cancer Drug Targets Disruption of Metabolic Pathways - Perspectives for the Treatment of Cancer
Current Cancer Drug Targets Multifunctional Anti-Cancer Nano-Platforms are Moving to Clinical Trials
Current Drug Metabolism Natural Medicine:The Genus Angelica
Current Medicinal Chemistry Transactivation of ErbB Receptors by Leptin in the Cardiovascular System: Mechanisms, Consequences and Target for Therapy
Current Pharmaceutical Design