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
-
Viral Elements Sense Tumorigenic Processes:Approaching Selective Cancer Therapy
Mini-Reviews in Medicinal Chemistry HPV Pathway Profiling: HPV Related Cervical Dysplasia and Carcinoma Studies
Current Pharmaceutical Design Multifunctional Nanoparticles, Nanocages and Degradable Polymers as a Potential Novel Generation of Non-Invasive Molecular and Cellular Imaging Systems
Recent Patents on Nanotechnology Stromal Derived Growth Factor-1alpha as a Beacon for Stem Cell Homing in Development and Injury
Current Neurovascular Research Biomarkers of Aging with Prognostic and Predictive Value in Non-Oncological Diseases
Current Medicinal Chemistry Oncogenic Fusion Tyrosine Kinases as Molecular Targets for Anti-Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry A Rationale for Inhibiting Progesterone-Related Pathways to Combat Breast Cancer
Current Cancer Drug Targets Targeted Therapies in Gynecologic Cancers
Current Cancer Drug Targets Novel VEGF-independent Strategies Targeting Tumor Vasculature: Clinical Aspects
Current Pharmaceutical Design Therapeutic Value of an Integrin Antagonist in Prostate Cancer
Current Drug Targets Ras Family Small GTPase-Mediated Neuroprotective Signaling in Stroke
Central Nervous System Agents in Medicinal Chemistry Stabilization of Folding Intermediate States from Alkaline Induced Unfolded State of Bovine Serum Fetuin in Trifluoroethanol and Acetonitrile
Protein & Peptide Letters Delivery of Peptidic Gonadotropin Releasing Hormone Antagonists
Current Drug Delivery The Metabolite Trimethylamine-N-Oxide is an Emergent Biomarker of Human Health
Current Medicinal Chemistry Transforming Growth Factor Beta in Pancreatic Cancer
Current Pharmaceutical Biotechnology Urokinase-type Plasminogen Activator (uPA) and its Receptor (uPAR): Development of Antagonists of uPA / uPAR Interaction and their Effects In Vitro and In Vivo
Current Pharmaceutical Design Designed Multiple Ligands for Cancer Therapy
Current Medicinal Chemistry Application of Proteomic Tools in Modern Nanotechnological Approaches Towards Effective Management of Neurodegenerative Disorders
Current Drug Metabolism Is there a Potential Immune Dysfunction with Anabolic Androgenic Steroid Use?: A Review
Mini-Reviews in Medicinal Chemistry Activities of Venom Proteins and Peptides with Possible Therapeutic Applications from Bees and WASPS
Protein & Peptide Letters