Abstract
Ovarian cancer is the leading cause of death among gynecological malignancies in the US and the poor outcome of current treatments necessitates the development of novel therapeutic strategies to fight against it. Epidemiological data indicate a positive association between higher latitude and ovarian cancer incidence and mortality rates, suggesting that vitamin D insufficiency may contribute to ovarian cancer development. Recent studies in the authors laboratory showed that multiple ovarian cancer cell lines respond to the active form of vitamin D, 1α,25-dihydroxyvitamin D3, for growth suppression. Mechanistic studies identified vitamin D-regulated genes with established functions in ovarian tumorigenesis as mediators for the growth suppression. While increased p27 protein stability and transcriptional up-regulation of GADD45 are responsible for 1α,25-dihydroxyvitamin D3-induced cell cycle arrest at G1/S and G2/M checkpoints, respectively, the hormone-induced apoptosis in ovarian cancer cells involves the down regulation of the mRNA stability of telomerase catalytic subunit. More importantly, preclinical studies showed that the synthetic vitamin D analog EB1089 effectively suppressed the growth of human ovarian tumor xenografts in mice. The tumor suppression is associated with an increase in apoptotic rate and a decrease in cell proliferation, suggesting that the molecular information can be translated into ovarian tumor suppression in animals. Based on these studies, we conclude that the vitamin D receptor that mediates these anti-tumor effects represents a novel molecular target for the development of new drugs for ovarian cancer. We predict that receptor-based drug discovery will lead to the successful development of more potent and safer vitamin D analogs for the treatment of this deadly disease.
Keywords: Vitamin D, VDR, ovarian cancer, p27, GADD45, telomerase, prevention, therapy
Current Cancer Drug Targets
Title: Vitamin D Receptor is a Novel Drug Target for Ovarian Cancer Treatment
Volume: 6 Issue: 3
Author(s): Xiaohui Zhang, Santo V. Nicosia and Wenlong Bai
Affiliation:
Keywords: Vitamin D, VDR, ovarian cancer, p27, GADD45, telomerase, prevention, therapy
Abstract: Ovarian cancer is the leading cause of death among gynecological malignancies in the US and the poor outcome of current treatments necessitates the development of novel therapeutic strategies to fight against it. Epidemiological data indicate a positive association between higher latitude and ovarian cancer incidence and mortality rates, suggesting that vitamin D insufficiency may contribute to ovarian cancer development. Recent studies in the authors laboratory showed that multiple ovarian cancer cell lines respond to the active form of vitamin D, 1α,25-dihydroxyvitamin D3, for growth suppression. Mechanistic studies identified vitamin D-regulated genes with established functions in ovarian tumorigenesis as mediators for the growth suppression. While increased p27 protein stability and transcriptional up-regulation of GADD45 are responsible for 1α,25-dihydroxyvitamin D3-induced cell cycle arrest at G1/S and G2/M checkpoints, respectively, the hormone-induced apoptosis in ovarian cancer cells involves the down regulation of the mRNA stability of telomerase catalytic subunit. More importantly, preclinical studies showed that the synthetic vitamin D analog EB1089 effectively suppressed the growth of human ovarian tumor xenografts in mice. The tumor suppression is associated with an increase in apoptotic rate and a decrease in cell proliferation, suggesting that the molecular information can be translated into ovarian tumor suppression in animals. Based on these studies, we conclude that the vitamin D receptor that mediates these anti-tumor effects represents a novel molecular target for the development of new drugs for ovarian cancer. We predict that receptor-based drug discovery will lead to the successful development of more potent and safer vitamin D analogs for the treatment of this deadly disease.
Export Options
About this article
Cite this article as:
Zhang Xiaohui, Nicosia V. Santo and Bai Wenlong, Vitamin D Receptor is a Novel Drug Target for Ovarian Cancer Treatment, Current Cancer Drug Targets 2006; 6 (3) . https://dx.doi.org/10.2174/156800906776842939
DOI https://dx.doi.org/10.2174/156800906776842939 |
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
-
Application of Liposomes in Cancer Therapy: An Assessment of the Advancement of Technology Through Patent Documents
Recent Patents on Nanotechnology Mesenchymal Stem Cells: Key Actors in Tumor Niche
Current Stem Cell Research & Therapy Doxycycline as Potential Anti-cancer Agent
Anti-Cancer Agents in Medicinal Chemistry Genes that Modulate the Sensitivity for Anti-Microtubule Drug-Mediated Chemotherapy
Current Cancer Drug Targets Current and Potential Treatments for Cervical Cancer
Current Cancer Drug Targets A Scientometrics Analysis and Visualization of Depressive Disorder
Current Neuropharmacology Genistein Potentiates the Anti-cancer Effects of Gemcitabine in Human Osteosarcoma via the Downregulation of Akt and Nuclear Factor-κB Pathway
Anti-Cancer Agents in Medicinal Chemistry Radiolabeling Methods and Nuclear Imaging Techniques in the Design of New Polymeric Carriers for Cancer Therapy
Current Applied Polymer Science The MRP Family and Anticancer Drug Metabolism
Current Drug Metabolism Stem Cell Differentiation Stage Factors from Zebrafish Embryo: A Novel Strategy to Modulate the Fate of Normal and Pathological Human (Stem) Cells
Current Pharmaceutical Biotechnology TNFR1 Regulates Ovarian Cancer Cell Tumorigenicity Through PIK3CB-p110Beta
Current Molecular Medicine The Nutrigenetics and Pharmacogenetics of Vitamin D Pathways
Current Pharmacogenomics and Personalized Medicine Recent Developments in Nanoparticle Based Targeted Delivery of Chemotherapeutics
Current Bioactive Compounds Anti-Metastatics: An Overview of Drug Candidates in Current Pipelines
Current Pharmaceutical Design Targeted Ultrasound Imaging of Cancer: An Emerging Technology on its Way to Clinics
Current Pharmaceutical Design Histone Deacetylase Inhibitors in Cancer Therapy: New Compounds and Clinical Update of Benzamide-Type Agents
Current Topics in Medicinal Chemistry Effective Strategies and Applications of Dendrimers in the Treatment of Ovarian Cancer
Current Pharmaceutical Design Immune Checkpoint Inhibitors and Cardiac Toxicity: An Emerging Issue
Current Medicinal Chemistry Novel and Emerging Drugs for Rarer Chronic Lymphoid Leukaemias
Current Cancer Drug Targets Targeting Heat Shock Proteins in Tauopathies
Current Alzheimer Research