Abstract
Objective: We found a novel marine drug, SZ–685C, that was isolated from the secondary metabolites of a mangrove endophytic fungus (No. 1403) collected from the South China Sea, which has been reported to inhibit the proliferation of certain tumor cells. However, its anticancer mechanism remains unknown. The aims of this study were to observe the effectiveness of SZ–685C on pituitary adenoma cells and determine the underlying mechanisms of action.
Methods: A rat prolactinoma cell line, MMQ, was used in this study. A dose escalation of SZ–685C was performed on this cell line, and cell viability was assessed using an MTT assay. Hoechst 33342, Annexin V–FITC/PI, TUNEL staining and flow cytometry were used to evaluate the extent of apoptosis at each concentration of SZ–685C. The effect of SZ–685C on prolactin expression was also evaluated using RT–PCR and immunoblotting. Quantitative RT–PCR was used to detect the expression of miR–200c in SZ–685C–stimulated MMQ cells and pituitary adenoma tissues. This miRNA was then overexpressed in MMQ cells via transfection of a miR–200c mimic to identify the mechanism underling the anti–tumor effect of SZ–685C.
Results: SZ–685C inhibited MMQ cell growth in a dose–dependent manner but showed little toxicity toward rat pituitary cells (RPCs). The IC50s of SZ–685C in MMQ cells and RPCs were 13.2 ± 1.3 mM and 49.1 ± 11.5 mM, respectively, which was statistically significant. Increasing numbers of apoptotic cells were observed in response to escalating concentrations of SZ–685C, and the expression level of prolactin (PRL) was inhibited. Nevertheless, the level of PRL mRNA was unchanged. Additionally, miR–200c was upregulated in MMQ cells compared with RPCs, and downregulation of miR– 200c was observed in SZ–685C–treated MMQ cells. Furthermore, the overexpression of miR–200c weakened the effect of SZ–685C–induced apoptosis of MMQ cells.
Conclusions: Our results suggest that SZ–685C induces MMQ cell apoptosis in a miR–200c–dependent manner. Therefore, SZ–685C might be a useful alternative treatment for pituitary adenoma.
Keywords: Pituitary adenoma, marine drug, SZ–685C, apoptosis, microRNA, miR–200c, prolactinoma, MMQ cell, mangrove endophytic fungus, treatment
Current Medicinal Chemistry
Title:A Novel Marine Drug, SZ–685C, Induces Apoptosis of MMQ Pituitary Tumor Cells by Downregulating miR–200c
Volume: 20 Issue: 16
Author(s): C.–H. Chen, W.–W. Xiao, X.–B. Jiang, J.–W. Wang, Z.–G. Mao, N. Lei, X. Fan, B.–B. Song, C.–X. Liao, H.–J. Wang, Z.–G. She and Y.–H. Zhu
Affiliation:
Keywords: Pituitary adenoma, marine drug, SZ–685C, apoptosis, microRNA, miR–200c, prolactinoma, MMQ cell, mangrove endophytic fungus, treatment
Abstract: Objective: We found a novel marine drug, SZ–685C, that was isolated from the secondary metabolites of a mangrove endophytic fungus (No. 1403) collected from the South China Sea, which has been reported to inhibit the proliferation of certain tumor cells. However, its anticancer mechanism remains unknown. The aims of this study were to observe the effectiveness of SZ–685C on pituitary adenoma cells and determine the underlying mechanisms of action.
Methods: A rat prolactinoma cell line, MMQ, was used in this study. A dose escalation of SZ–685C was performed on this cell line, and cell viability was assessed using an MTT assay. Hoechst 33342, Annexin V–FITC/PI, TUNEL staining and flow cytometry were used to evaluate the extent of apoptosis at each concentration of SZ–685C. The effect of SZ–685C on prolactin expression was also evaluated using RT–PCR and immunoblotting. Quantitative RT–PCR was used to detect the expression of miR–200c in SZ–685C–stimulated MMQ cells and pituitary adenoma tissues. This miRNA was then overexpressed in MMQ cells via transfection of a miR–200c mimic to identify the mechanism underling the anti–tumor effect of SZ–685C.
Results: SZ–685C inhibited MMQ cell growth in a dose–dependent manner but showed little toxicity toward rat pituitary cells (RPCs). The IC50s of SZ–685C in MMQ cells and RPCs were 13.2 ± 1.3 mM and 49.1 ± 11.5 mM, respectively, which was statistically significant. Increasing numbers of apoptotic cells were observed in response to escalating concentrations of SZ–685C, and the expression level of prolactin (PRL) was inhibited. Nevertheless, the level of PRL mRNA was unchanged. Additionally, miR–200c was upregulated in MMQ cells compared with RPCs, and downregulation of miR– 200c was observed in SZ–685C–treated MMQ cells. Furthermore, the overexpression of miR–200c weakened the effect of SZ–685C–induced apoptosis of MMQ cells.
Conclusions: Our results suggest that SZ–685C induces MMQ cell apoptosis in a miR–200c–dependent manner. Therefore, SZ–685C might be a useful alternative treatment for pituitary adenoma.
Export Options
About this article
Cite this article as:
Chen C.–H., Xiao W.–W., Jiang X.–B., Wang J.–W., Mao Z.–G., Lei N., Fan X., Song B.–B., Liao C.–X., Wang H.–J., She Z.–G. and Zhu Y.–H., A Novel Marine Drug, SZ–685C, Induces Apoptosis of MMQ Pituitary Tumor Cells by Downregulating miR–200c, Current Medicinal Chemistry 2013; 20 (16) . https://dx.doi.org/10.2174/0929867311320160007
DOI https://dx.doi.org/10.2174/0929867311320160007 |
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
-
Thiomers, Mucoadhesion and Oral Delivery of Biomacromolecules
Current Drug Therapy Lactobacillus GG (LGG) Peptides Can Inhibit Antibiotic-Resistant Bacteria Growth
Anti-Infective Agents in Medicinal Chemistry New Insights Toward Nanostructured Drug Delivery of Plant-Derived Polyphenol Compounds: Cancer Treatment and Gene Expression Profiles
Current Cancer Drug Targets Clinical Trials with Oncolytic Measles Virus: Current Status and Future Prospects
Current Cancer Drug Targets The ATP-driven Hsp60 Machinery: Biological and Clinical Implications
Current Immunology Reviews (Discontinued) The Anti-Oxidant Properties of Isothiocyanates: A Review
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Oncogene Expression Modulation in Cancer Cell Lines by DNA G-Quadruplex-Interactive Small Molecules
Current Medicinal Chemistry Anticancer Peptides and Proteins: A Panoramic View
Protein & Peptide Letters Epithelial Mesenchymal Transition in Cancer Progression: Prev entive Phytochemicals
Recent Patents on Anti-Cancer Drug Discovery Small Molecule Complementarity As A Source of Novel Pharmaceutical Agents and Combination Therapies
Current Pharmaceutical Design Flavonoid Derivatives Targeting BCR-ABL Kinase: Semisynthesis, Molecular Dynamic Simulations and Enzymatic Inhibition
Current Topics in Medicinal Chemistry A Systematic Review of the Uterine Relaxant Effect of Herbal Sources
Current Pharmaceutical Biotechnology Blockade of Insulin-Like Growth Factor Type-1 Receptor with Cixutumumab (IMC-A12): A Novel Approach to Treatment for Multiple Cancers
Current Drug Targets Genitourinary Tumors: Update on Molecular Biomarkers for Diagnosis, Prognosis and Prediction of Response to Therapy
Current Drug Metabolism Cellular Changes, Molecular Pathways and the Immune System Following Photodynamic Treatment
Current Medicinal Chemistry Spectrum of Unusual Imaging Findings of Metastatic Lesions from Gastric Cancer
Current Medical Imaging Pros and Cons of Medical Cannabis use by People with Chronic Brain Disorders
Current Neuropharmacology Role of microRNA Deregulation in Breast Cancer Cell Chemoresistance and Stemness
Current Medicinal Chemistry Hibiscus Sabdariffa Linnaeus (Malvaceae), Curcumin and Resveratrol as Alternative Medicinal Agents Against Metabolic Syndrome
Cardiovascular & Hematological Agents in Medicinal Chemistry Transcription Factors as Targets for Cancer Therapy: AP-1 a Potential Therapeutic Target
Current Cancer Therapy Reviews