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
-
Systems Medicine Approaches to Improving Understanding, Treatment, and Clinical Management of Neuroendocrine Prostate Cancer
Current Pharmaceutical Design Hereditary Breast Cancer in Sub-Saharan Africa
Current Women`s Health Reviews Apoptosis: Potential Therapeutic Targets for New Drug Discovery
Current Medicinal Chemistry Synthesis and Evaluation of Biological Activities of a Series of (6-substitutedbenzothiazol-2-yl)acrylamides
Medicinal Chemistry Olive Oil and Apoptosis of Cancer Cells
Current Nutrition & Food Science Sesterterpenoids with Anticancer Activity
Current Medicinal Chemistry Filling the Gaps between the In Vivo and In Vitro Microenvironment: Engineering of Spheroids for Stem Cell Technology
Current Stem Cell Research & Therapy The Integrative Network of Gene Expression, MicroRNA, Methylation and Copy Number Variation in Colon and Rectal Cancer
Current Bioinformatics Biotransformations of Prenylated Hop Flavonoids for Drug Discovery and Production
Current Drug Metabolism A Closer Look at Protein Transduction Domains as a Tool in Drug Delivery
Current Nanoscience Eliminating Ovarian Cancer Stem Cells: A Potential Therapeutic Target for Ovarian Cancer Chemoresistance
Current Protein & Peptide Science Enhancement of the Effect of Methyl Pyropheophorbide-a-Mediated Photodynamic Therapy was Achieved by Increasing ROS through Inhibition of Nrf2-HO-1 or Nrf2-ABCG2 Signaling
Anti-Cancer Agents in Medicinal Chemistry New Peptidic GnRH Antagonists Offer a Broad Range of Therapeutic Applications
Letters in Drug Design & Discovery Novel Therapeutic Strategies Against Cancer: Marine-derived Drugs May Be the Answer?
Anti-Cancer Agents in Medicinal Chemistry Transcription Factor WT1 and Promoter CpG Hypomethylation Coactivate HOXA10 Expression in Ovarian Cancer
Current Pharmaceutical Design Nanoparticle Engineering Enhances Anticancer Efficacy of Andrographolide in MCF-7 Cells and Mice Bearing EAC
Current Pharmaceutical Biotechnology Betulin-Betulinic Acid Natural Product Based Analogs as Anti-Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry Novel and Emerging Targeted Therapies of Colorectal Cancer
Current Clinical Pharmacology Dysregulation of LncRNAs in Placenta and Pathogenesis of Preeclampsia
Current Drug Targets Prospects for Plant-Derived Chemopreventive Agents Exhibiting Multiple Mechanisms of Action
Current Medicinal Chemistry - Anti-Cancer Agents