Abstract
Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in endometrial cancers and ovarian cancers, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. Clonogenic assay in soft agar and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that many endometrial and ovarian cancer cell lines were sensitive to the growth inhibitory effect of HDAC inhibitors (HDACIs), although normal endometrial epithelial cells were viable after the treatment with the same doses of HDACIs that induced growth inhibition of endometrial and ovarian cancer cells. Cell cycle analysis indicated that their exposure to HDACIs decreased the proportion of cells in the S-phase and increased the proportion in the G0/G1 phases and/or G2/M phases of the cell cycle. Induction of apoptosis was confirmed by TUNEL assay, annexin V staining of externalized phosphatidylserine, and loss of the transmembrane potential of mitochondria. This induction occurred in concert with altered expression of genes related to cell growth, malignant phenotype, and apoptosis. In nude mice experiments, valproic acid significantly inhibited human endometrial and ovarian tumor growth without toxic sideeffects. Although there are few clinical trials on these cancers, some clinical trials showed that HDACIs in well tolerated doses have significant antitumoral activities in another cancers. These results raise the possibility that HDACIs may prove particularly effective in the treatment of endometrial cancers and ovarian cancers.
Keywords: Histone deacetylase inhibitors, cell cycle, apoptosis, acetylation, endometrial cancer, ovarian cancer
Current Medicinal Chemistry
Title: Human Endometrial and Ovarian Cancer Cells: Histone Deacetylase Inhibitors Exhibit Antiproliferative Activity, Potently Induce Cell Cycle Arrest, and Stimulate Apoptosis
Volume: 14 Issue: 24
Author(s): Noriyuki Takai, Hisashi Narahara, Noriyuki Takai and Hisashi Narahara
Affiliation:
Keywords: Histone deacetylase inhibitors, cell cycle, apoptosis, acetylation, endometrial cancer, ovarian cancer
Abstract: Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in endometrial cancers and ovarian cancers, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. Clonogenic assay in soft agar and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that many endometrial and ovarian cancer cell lines were sensitive to the growth inhibitory effect of HDAC inhibitors (HDACIs), although normal endometrial epithelial cells were viable after the treatment with the same doses of HDACIs that induced growth inhibition of endometrial and ovarian cancer cells. Cell cycle analysis indicated that their exposure to HDACIs decreased the proportion of cells in the S-phase and increased the proportion in the G0/G1 phases and/or G2/M phases of the cell cycle. Induction of apoptosis was confirmed by TUNEL assay, annexin V staining of externalized phosphatidylserine, and loss of the transmembrane potential of mitochondria. This induction occurred in concert with altered expression of genes related to cell growth, malignant phenotype, and apoptosis. In nude mice experiments, valproic acid significantly inhibited human endometrial and ovarian tumor growth without toxic sideeffects. Although there are few clinical trials on these cancers, some clinical trials showed that HDACIs in well tolerated doses have significant antitumoral activities in another cancers. These results raise the possibility that HDACIs may prove particularly effective in the treatment of endometrial cancers and ovarian cancers.
Export Options
About this article
Cite this article as:
Takai Noriyuki, Narahara Hisashi, Takai Noriyuki and Narahara Hisashi, Human Endometrial and Ovarian Cancer Cells: Histone Deacetylase Inhibitors Exhibit Antiproliferative Activity, Potently Induce Cell Cycle Arrest, and Stimulate Apoptosis, Current Medicinal Chemistry 2007; 14 (24) . https://dx.doi.org/10.2174/092986707782023299
DOI https://dx.doi.org/10.2174/092986707782023299 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
The Genomics of Colorectal Cancer: State of the Art
Current Genomics Tailored Angiogenesis Inhibition in Cancer Therapy: Respecting the Heart to Improve the Net Outcome
Current Signal Transduction Therapy Membrane Disrupting Lytic Peptides for Cancer Treatments
Current Pharmaceutical Design Pharmacological Inhibitors of NAD Biosynthesis as Potential An ticancer Agents
Recent Patents on Anti-Cancer Drug Discovery Procathepsin D as a Tumor Marker, Anti-Cancer Drug or Screening Agent
Anti-Cancer Agents in Medicinal Chemistry Recent Advances in the Rationale Design of GPER Ligands
Current Medicinal Chemistry Clomiphene Citrate, Metformin or Both for Ovulation Induction in Therapy Naïve Women with Polycystic Ovary Syndrome (PCOS)? A Descriptive Review
Current Drug Therapy Mining the Dark Matter of the Cancer Proteome for Novel Biomarkers
Current Cancer Therapy Reviews Structural and Functional Diversity of Estrogen Receptor Ligands
Current Topics in Medicinal Chemistry The Functional Role of Long Non-coding RNA UCA1 in Human Multiple Cancers: a Review Study
Current Molecular Medicine Multifunctional Materials for Cancer Therapy: From Antitumoral Agents to Innovative Administration
Current Organic Chemistry Hypertension, Anti-Hypertensive Therapy and Neoplasia
Current Pharmaceutical Design Inhibition of TGF- Signaling for the Treatment of Tumor Metastasis and Fibrotic Diseases
Current Signal Transduction Therapy Reproductive and Endocrine Effects of p-Nonylphenol and Methoxychlor: A Review
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Expression and Function of Angiomodulating Cytokines in Rheumatoid Arthritis and Experimental Arthritis: Important Therapeutic Targets
Current Immunology Reviews (Discontinued) Mesenchymal Stem Cells as a Source of Dopaminergic Neurons: A Potential Cell Based Therapy for Parkinson's Disease
Current Stem Cell Research & Therapy Inhibition of Early Upstream Events in Prodromal Alzheimer’s Disease by Use of Targeted Antioxidants
Current Aging Science Finding Novel Anti-carcinomas Compounds by Targeting SFRP4 Through Molecular Modeling, Docking and Dynamic Simulation Studies
Current Computer-Aided Drug Design Receptor Tryosine Kinase Inhibitors as Potent Weapons in War Against Cancers
Current Pharmaceutical Design Therapeutic Potential of Natural Compounds that Regulate the Activity of Protein Kinase C
Current Medicinal Chemistry