Abstract
Identification of novel chemotherapeutic agents from traditional medicines and elucidation of the molecular basis of their anticancer effects are critical and urgently needed for modern pharmacotherapy. We previously found that analogs of the compounds present in Valeriana jatamansi, a traditional medicine used to treat mental disorders, possess notable antitumor properties; however, the underlying molecular mechanisms have not been fully demonstrated. In this study, we evaluated the anticancer effects of IVHD-valtrate, one of the most active Valeriana jatamansi derivatives, against human ovarian cancer cells in vitro and in vivo. IVHD-valtrate inhibited the growth and proliferation of the A2780 and OVCAR-3 ovarian cancer cell lines in a concentration-dependent manner, while relatively low cytotoxicity to immortalized non-tumorigenic human ovarian surface epithelial cells (IOSE-144) was observed. Treatment with IVHDvaltrate arrested the ovarian cancer cells in the G2/M phase and induced apoptosis, and significantly suppressed the growth of A2780 and OVCAR3 xenograft tumors in a dose-dependent manner. The detailed in vitro and in vivo study on the molecular mechanisms of this compound demonstrated that IVHD-valtrate exposure modulated the expression of numerous molecules involved in cell cycle progression and apoptosis regardless of p53 status, leading to increase the level of p53, Rb, p21, p27 and decrease Mdm2, E2F1, Cyclin B1, Cdc25C and Cdc2. It also down-regulated Bcl-2/Bax and Bcl-2/Bad ratio and enhanced the cleavage of PARP and Caspases.
Our preclinical results indicated IVHD-valtrate is a potential therapeutic agent for ovarian cancer, providing a basis for development of the compound as a novel chemotherapeutic agent.
Keywords: IVHD-valtrate, ovarian cancer, apoptosis, cell cycle, chemotherapeutic agent.
Current Cancer Drug Targets
Title:Valeriana jatamansi Constituent IVHD-valtrate As a Novel Therapeutic Agent to Human Ovarian Cancer: in vitro and in vivo Activities and Mechanisms
Volume: 13 Issue: 4
Author(s): Xiaoguang Li, Tao Chen, Sheng Lin, Jing Zhao, Peizhan Chen, Qian Ba, He Guo, Yanling Liu, Jingquan Li, Ruiai Chu, Lei Shan, Weidong Zhang and Hui Wang
Affiliation:
Keywords: IVHD-valtrate, ovarian cancer, apoptosis, cell cycle, chemotherapeutic agent.
Abstract: Identification of novel chemotherapeutic agents from traditional medicines and elucidation of the molecular basis of their anticancer effects are critical and urgently needed for modern pharmacotherapy. We previously found that analogs of the compounds present in Valeriana jatamansi, a traditional medicine used to treat mental disorders, possess notable antitumor properties; however, the underlying molecular mechanisms have not been fully demonstrated. In this study, we evaluated the anticancer effects of IVHD-valtrate, one of the most active Valeriana jatamansi derivatives, against human ovarian cancer cells in vitro and in vivo. IVHD-valtrate inhibited the growth and proliferation of the A2780 and OVCAR-3 ovarian cancer cell lines in a concentration-dependent manner, while relatively low cytotoxicity to immortalized non-tumorigenic human ovarian surface epithelial cells (IOSE-144) was observed. Treatment with IVHDvaltrate arrested the ovarian cancer cells in the G2/M phase and induced apoptosis, and significantly suppressed the growth of A2780 and OVCAR3 xenograft tumors in a dose-dependent manner. The detailed in vitro and in vivo study on the molecular mechanisms of this compound demonstrated that IVHD-valtrate exposure modulated the expression of numerous molecules involved in cell cycle progression and apoptosis regardless of p53 status, leading to increase the level of p53, Rb, p21, p27 and decrease Mdm2, E2F1, Cyclin B1, Cdc25C and Cdc2. It also down-regulated Bcl-2/Bax and Bcl-2/Bad ratio and enhanced the cleavage of PARP and Caspases.
Our preclinical results indicated IVHD-valtrate is a potential therapeutic agent for ovarian cancer, providing a basis for development of the compound as a novel chemotherapeutic agent.
Export Options
About this article
Cite this article as:
Li Xiaoguang, Chen Tao, Lin Sheng, Zhao Jing, Chen Peizhan, Ba Qian, Guo He, Liu Yanling, Li Jingquan, Chu Ruiai, Shan Lei, Zhang Weidong and Wang Hui, Valeriana jatamansi Constituent IVHD-valtrate As a Novel Therapeutic Agent to Human Ovarian Cancer: in vitro and in vivo Activities and Mechanisms, Current Cancer Drug Targets 2013; 13 (4) . https://dx.doi.org/10.2174/1568009611313040009
DOI https://dx.doi.org/10.2174/1568009611313040009 |
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
-
Development of Genetic Testing for Breast, Ovarian and Colorectal Cancer Predisposition: A Step Closer to Targeted Cancer Prevention
Current Drug Targets Recent Approaches to Platinum(IV) Prodrugs: A Variety of Strategies for Enhanced Delivery and Efficacy
Current Pharmaceutical Design The SCF-type E3 Ubiquitin Ligases as Cancer Targets
Current Cancer Drug Targets Individualized Treatment Planning in Oncology: Role of PET and Radiolabelled Anticancer Drugs in Predicting Tumour Resistance
Current Pharmaceutical Design Recent Advances in Diagnostic and Therapeutic Approaches for Breast Cancer: A Comprehensive Review
Current Pharmaceutical Design Deregulation of HOX B13 Expression in Urinary Bladder Cancer Progression
Current Medicinal Chemistry Role of microRNAs in Hepatic Stellate Cells and Hepatic Fibrosis: An Update
Current Pharmaceutical Design How Much of Familial Breast Cancer Risk is Currently Explained by the Known Genes?
Current Women`s Health Reviews A Perspective on Stem Cells as Biological Systems that Produce Differentiated Osteoblasts and Odontoblasts
Current Stem Cell Research & Therapy Combination of Photodynamic Therapy with Anti-Cancer Agents
Current Medicinal Chemistry Recent Advances in Radiation Therapy of Cancer Cells: A Step towards an Experimental and Systems Biology Framework
Current Radiopharmaceuticals Gene Silencing in the Development of Personalized Cancer Treatment: The Targets, the Agents and the Delivery Systems
Current Gene Therapy Targeting the Akt Kinase to Modulate Survival, Invasiveness and Drug Resistance of Cancer Cells
Current Medicinal Chemistry Reversal of ABC Drug Transporter-Mediated Multidrug Resistance in Cancer Cells: Evaluation of Current Strategies
Current Molecular Pharmacology The Chemokine Receptor CXCR4 as a Therapeutic Target for Several Diseases
Mini-Reviews in Medicinal Chemistry Improving Cancer Chemotherapy with Modulators of ABC Drug Transporters
Current Drug Targets Recent Patents on Genes and Gene Sequences Useful for Developing Breast Cancer Detection Systems
Recent Patents on DNA & Gene Sequences Curcumin: A Promising Agent Targeting Cancer Stem Cells
Anti-Cancer Agents in Medicinal Chemistry Review of Procedures Used for the Extraction of Anti-Cancer Compounds from Tropical Plants
Anti-Cancer Agents in Medicinal Chemistry Working Hypothesis: Elimination of Cancer Stem Cells in Solid Tumors by Immuno-Gene Therapy Using Cancer Vaccines and Created-Inhibitory RNA
Current Cancer Therapy Reviews