Abstract
As the principal active ingredient in the Chinese herb Tripterygium wilfordii Hook.F (TwHF), triptolide has been shown to have very strong antitumor properties. The trimethylation of lysine 4 on histone H3 (H3K4me3) has been proposed to promote gene expression, and the accumulation of H3K4me3 at the transcriptional start sites of oncogenes is involved in carcinogenesis. To identify the association between the reduction of H3K4me3 and the apoptosis of MM cells induced by triptolide, we investigated the global patterns of H3K4me3 occupancy in the MM cell genome. Combined analyses using ChIP-on-chip and western blotting showed that H3K4me3 were highly enriched on the gene promoters of c-Myc and VEGFA and were associated with the up-regulation of both genes. Treatment of KM3 cells with triptolide and siRNA targeting ASH2L reduced the expression of c-Myc and VEGFA. These results suggest that triptolide can down-regulate c-Myc and VEGFA expression by blocking the accumulation of H3K4me3 on their promoters,and thus play an important role in anti-MM mechanism.
Keywords: Apoptosis, ASH2L, c-Myc, H3K4me3, Multiple myeloma, Triptolide, VEGFA.
Current Pharmaceutical Biotechnology
Title:Triptolide Induces Cell Apoptosis by Targeting H3K4me3 and Downstream Effector Proteins in KM3 Multiple Myeloma Cells
Volume: 17 Issue: 2
Author(s): Lu Wen, Yan Chen, Ling L. Zeng, Fei Zhao, Sha Yi, Li J. Yang, Ben P. Zhang, Jie Zhao, Zi C. Zhao and Chun Zhang
Affiliation:
Keywords: Apoptosis, ASH2L, c-Myc, H3K4me3, Multiple myeloma, Triptolide, VEGFA.
Abstract: As the principal active ingredient in the Chinese herb Tripterygium wilfordii Hook.F (TwHF), triptolide has been shown to have very strong antitumor properties. The trimethylation of lysine 4 on histone H3 (H3K4me3) has been proposed to promote gene expression, and the accumulation of H3K4me3 at the transcriptional start sites of oncogenes is involved in carcinogenesis. To identify the association between the reduction of H3K4me3 and the apoptosis of MM cells induced by triptolide, we investigated the global patterns of H3K4me3 occupancy in the MM cell genome. Combined analyses using ChIP-on-chip and western blotting showed that H3K4me3 were highly enriched on the gene promoters of c-Myc and VEGFA and were associated with the up-regulation of both genes. Treatment of KM3 cells with triptolide and siRNA targeting ASH2L reduced the expression of c-Myc and VEGFA. These results suggest that triptolide can down-regulate c-Myc and VEGFA expression by blocking the accumulation of H3K4me3 on their promoters,and thus play an important role in anti-MM mechanism.
Export Options
About this article
Cite this article as:
Wen Lu, Chen Yan, Zeng L. Ling, Zhao Fei, Yi Sha, Yang J. Li, Zhang P. Ben, Zhao Jie, Zhao C. Zi and Zhang Chun, Triptolide Induces Cell Apoptosis by Targeting H3K4me3 and Downstream Effector Proteins in KM3 Multiple Myeloma Cells, Current Pharmaceutical Biotechnology 2016; 17 (2) . https://dx.doi.org/10.2174/1389201016666150930115555
DOI https://dx.doi.org/10.2174/1389201016666150930115555 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...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
-
New Approaches in Glioblastoma Multiforme: The Potential Role of Immune- check Point Inhibitors
Current Cancer Drug Targets The Potential and Limitations of p38MAPK as a Drug Target for the Treatment of Hematological Malignancies
Current Drug Targets Doxorubicin: The Good, the Bad and the Ugly Effect
Current Medicinal Chemistry Inflammation and Cancer: When NF-κB Amalgamates the Perilous Partnership
Current Cancer Drug Targets Bortezomib: Proteasome Inhibition as a Novel Mechanism of Cancer Therapy-Implications for Hematological Malignancies
Letters in Drug Design & Discovery Survivin Modulators: An Updated Patent Review (2011 - 2015)
Recent Patents on Anti-Cancer Drug Discovery Use of Systemic Proteasome Inhibition as an Immune-Modulating Agent in Disease
Endocrine, Metabolic & Immune Disorders - Drug Targets Antiphospholipid Antibody-Mediated Thrombotic Mechanisms in Antiphospholipid Syndrome: Towards Pathophysiology-Based Treatment
Current Pharmaceutical Design Anti-Cancer Activity of Curcumin on Multiple Myeloma
Anti-Cancer Agents in Medicinal Chemistry Encapsulation of Imatinib in Targeted KIT-5 Nanoparticles for Reducing its Cardiotoxicity and Hepatotoxicity
Anti-Cancer Agents in Medicinal Chemistry Induction of Regulatory T Cells by Dendritic Cells through Indoleamine 2,3- dioxygenase: A Potent Mechanism of Acquired Peripheral Tolerance
Current Medicinal Chemistry Recent Patents on Live Bacteria and their Products as Potential Anticancer Agents
Recent Patents on Anti-Cancer Drug Discovery Stem Cells, Cancer, Liver, and Liver Cancer Stem Cells: Finding a Way Out of the Labyrinth...
Current Cancer Drug Targets Cancer Prevention with Promising Natural Products: Mechanisms of Action and Molecular Targets
Anti-Cancer Agents in Medicinal Chemistry Predicting Toxicity: Biomarkers and the Value of the Patient's Opinion
Current Pharmaceutical Design Nano Anti-Cancer Drugs: Pros and Cons and Future Perspectives
Current Cancer Drug Targets Antifungal Agents in Hematopoietic Stem Cell Transplantation
Current Pharmaceutical Design Abelson Tyrosine-Protein Kinase 1 as Principal Target for Drug Discovery Against Leukemias. Role of the Current Computer-Aided Drug Design Methodologies
Current Topics in Medicinal Chemistry Adhesion Molecules and Kinases Involved in γ δ T Cells Migratory Pathways:Implications for Viral and Autoimmune Diseases
Current Medicinal Chemistry Emerging Molecular Functions of MicroRNA-9: Cancer Pathology and Therapeutic Implications
Anti-Cancer Agents in Medicinal Chemistry