Abstract
Platycodin D (PD), a major saponin derived from Platycodin grandiflorum, exerted cytotoxicity against prostate cancer cell lines (PC3, DU145 and LNCaP cells) with IC50 values in the range of 11.17 to 26.13μmol/L, whereas RWPE-1cells (a non-malignant human prostate epithelial cell line) were not significantly affected. A further study in these cell lines showed that PD could potently affect cell proliferation (indicated by the bromodeoxyuridine assay), induce cell apoptosis (determined by Annexin V-FITC flow cytometry) and cause cell cycle arrest (indicated by PI staining). After being treated with PD for 48 hours, DU145 and LNCaP cells were arrested in the G0 /G1 phase, and PC3 cells were arrested in the G2/M phase. A Western blotting analysis indicated that PD increased the expression of the FOXO3a transcription factor, decreased the expression of p-FOXO3a and MDM2 and increased the expression of FOXO-responsive genes, p21 and p27. MDM2 silencing (transiently by siRNA-MDM2) increased the PD-induced FOXO3a protein expression, while MDM2 overexpression (in cells transiently transfected with a pcDNA3-MDM2 plasmid) decreased the PD-induced expression of the FOXO3a protein. Moreover, PD dose-dependently inhibited the growth of PC3 xenograft tumors in BALB/c nude mice. A Western blotting analysis of the excised xenograft tumors indicated that similar changes in protein expression also occurred in vivo. These results suggest that PD exhibits significant activity against prostate cancer in vitro and in vivo. The FOXO3a transcription factor appears to be involved in the activity of PD. Together, all of these findings provide a basis for the future development of this agent for human prostate cancer therapy.
Keywords: Cell cycle, FOXO3a, MDM2, Platycodin D, prostate cancer.
Current Cancer Drug Targets
Title:Platycodin D Induces Tumor Growth Arrest by Activating FOXO3a Expression in Prostate Cancer in vitro and in vivo
Volume: 14 Issue: 9
Author(s): Rui Zhou, Zongliang Lu, Kai Liu, Jing Guo, Jie Liu, Yong Zhou, Jian Yang, Mantian Mi and Hongxia Xu
Affiliation:
Keywords: Cell cycle, FOXO3a, MDM2, Platycodin D, prostate cancer.
Abstract: Platycodin D (PD), a major saponin derived from Platycodin grandiflorum, exerted cytotoxicity against prostate cancer cell lines (PC3, DU145 and LNCaP cells) with IC50 values in the range of 11.17 to 26.13μmol/L, whereas RWPE-1cells (a non-malignant human prostate epithelial cell line) were not significantly affected. A further study in these cell lines showed that PD could potently affect cell proliferation (indicated by the bromodeoxyuridine assay), induce cell apoptosis (determined by Annexin V-FITC flow cytometry) and cause cell cycle arrest (indicated by PI staining). After being treated with PD for 48 hours, DU145 and LNCaP cells were arrested in the G0 /G1 phase, and PC3 cells were arrested in the G2/M phase. A Western blotting analysis indicated that PD increased the expression of the FOXO3a transcription factor, decreased the expression of p-FOXO3a and MDM2 and increased the expression of FOXO-responsive genes, p21 and p27. MDM2 silencing (transiently by siRNA-MDM2) increased the PD-induced FOXO3a protein expression, while MDM2 overexpression (in cells transiently transfected with a pcDNA3-MDM2 plasmid) decreased the PD-induced expression of the FOXO3a protein. Moreover, PD dose-dependently inhibited the growth of PC3 xenograft tumors in BALB/c nude mice. A Western blotting analysis of the excised xenograft tumors indicated that similar changes in protein expression also occurred in vivo. These results suggest that PD exhibits significant activity against prostate cancer in vitro and in vivo. The FOXO3a transcription factor appears to be involved in the activity of PD. Together, all of these findings provide a basis for the future development of this agent for human prostate cancer therapy.
Export Options
About this article
Cite this article as:
Zhou Rui, Lu Zongliang, Liu Kai, Guo Jing, Liu Jie, Zhou Yong, Yang Jian, Mi Mantian and Xu Hongxia, Platycodin D Induces Tumor Growth Arrest by Activating FOXO3a Expression in Prostate Cancer in vitro and in vivo, Current Cancer Drug Targets 2014; 14 (9) . https://dx.doi.org/10.2174/1568009614666141128104642
DOI https://dx.doi.org/10.2174/1568009614666141128104642 |
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
-
Potentials of Polymeric Nanoparticle as Drug Carrier for Cancer Therapy: With a Special Reference to Pharmacokinetic Parameters
Current Drug Metabolism Circumventing Immune Tolerance Through Epigenetic Modification
Current Pharmaceutical Design Obstructive Sleep Apnoea Syndrome and Diabetes. Fortuitous Association or Interaction?
Current Diabetes Reviews An Uncommon Case of Symptomatic Multiple Meningiomas with Bilateral Compressive Optic Neuropathy Rapidly Induced under Cyprotero ne Acetate Treatment
Current Drug Safety Boronic Acid-based Enzyme Inhibitors: A Review of Recent Progress
Current Medicinal Chemistry Analysis of Microarray Gene Expression Data
Current Bioinformatics MUC1 is a Promising Therapeutic Target for Prostate Cancer Therapy
Current Cancer Drug Targets Repeated Restraint and Nerve Growth Factor Administration in Male and Female Mice: Effect on Sympathetic and Cardiovascular Mediators of the Stress Response
Current Neurovascular Research The RNA Binding Protein HuR: a Promising Drug Target for Anticancer Therapy
Current Cancer Drug Targets Photoacoustic Detection and Imaging of Cancer Using Nanoparticles as Optical Contrast Agents
Recent Patents on Nanomedicine The Role of Cytokine Network in the Pathophysiology of Schizophrenia
Current Psychiatry Reviews Evaluation of Effect of Ligand on Cellular Internalization: A Comparative Study of Nanoparticles and Multifunctional Nanoparticles on MDA-MB-231 Cells
Current Nanoscience Information Theoretic Entropy for Molecular Classification: Oxadiazolamines as Potential Therapeutic Agents
Current Computer-Aided Drug Design Peptide-Based Anticancer Vaccines: Recent Advances and Future Perspectives
Current Medicinal Chemistry Potential of DNMT and its Epigenetic Regulation for Lung Cancer Therapy
Current Genomics 2-Arylbenzothiazole as a Privileged Scaffold in Drug Discovery
Current Medicinal Chemistry Epigallocatechin-3-gallate Increases RXRγ-mediated Pro-apoptotic and Anti-invasive Effects in Gastrointestinal Cancer Cell Lines
Current Cancer Drug Targets Oxazole-Based Compounds As Anticancer Agents
Current Medicinal Chemistry Editorial: Stay in Excellence
Current Molecular Medicine Nanotechnology and Antioxidant Therapy: An Emerging Approach for Neurodegenerative Diseases
Current Medicinal Chemistry