Abstract
Thiol-containing antioxidant systems play an important role in regulating cellular redox homeostasis. Several anti-cancer agents act by targeting these systems by inducing the production of reactive oxygen species (ROS). Our earlier studies have shown that Eriocalyxin B (EriB), a diterpenoid isolated from Isodon eriocalyx, possesses anti-pancreatic tumour activities in vitro and in vivo. The present study further demonstrated that only thiol-containing antioxidants, N-acetylcysteine (NAC) or dithiothreitol (DTT), inhibited EriB-induced cytotoxicity and apoptosis. EriB suppressed the glutathione and thioredoxin antioxidant systems, thus increasing the intracellular ROS levels and regulating the MAPK, NFκB pathways. Treatment with EriB depleted the intracellular thiol-containing proteins in CAPAN-2 cells. In vivo studies also showed that EriB treatment (2.5 mg/kg) reduced the pancreatic tumour weights significantly in nude mice with increased superoxide levels. Taken together, our results shed important new light on the molecular mechanisms of EriB acting as an apoptogenic agent and its therapeutic potential for pancreatic cancer.
Keywords: Apoptosis, eriocalyxin B, pancreatic cancer, reactive oxygen species, thiols.
Current Molecular Medicine
Title:Eriocalyxin B-Induced Apoptosis in Pancreatic Adenocarcinoma Cells Through Thiol-Containing Antioxidant Systems and Downstream Signalling Pathways
Volume: 14 Issue: 5
Author(s): L. Li, G.G.L. Yue, J.X. Pu, H.D. Sun, K.P. Fung, P.C. Leung, Q.B. Han, C.B.S. Lau and P.S. Leung
Affiliation:
Keywords: Apoptosis, eriocalyxin B, pancreatic cancer, reactive oxygen species, thiols.
Abstract: Thiol-containing antioxidant systems play an important role in regulating cellular redox homeostasis. Several anti-cancer agents act by targeting these systems by inducing the production of reactive oxygen species (ROS). Our earlier studies have shown that Eriocalyxin B (EriB), a diterpenoid isolated from Isodon eriocalyx, possesses anti-pancreatic tumour activities in vitro and in vivo. The present study further demonstrated that only thiol-containing antioxidants, N-acetylcysteine (NAC) or dithiothreitol (DTT), inhibited EriB-induced cytotoxicity and apoptosis. EriB suppressed the glutathione and thioredoxin antioxidant systems, thus increasing the intracellular ROS levels and regulating the MAPK, NFκB pathways. Treatment with EriB depleted the intracellular thiol-containing proteins in CAPAN-2 cells. In vivo studies also showed that EriB treatment (2.5 mg/kg) reduced the pancreatic tumour weights significantly in nude mice with increased superoxide levels. Taken together, our results shed important new light on the molecular mechanisms of EriB acting as an apoptogenic agent and its therapeutic potential for pancreatic cancer.
Export Options
About this article
Cite this article as:
Li L., Yue G.G.L., Pu J.X., Sun H.D., Fung K.P., Leung P.C., Han Q.B., Lau C.B.S. and Leung P.S., Eriocalyxin B-Induced Apoptosis in Pancreatic Adenocarcinoma Cells Through Thiol-Containing Antioxidant Systems and Downstream Signalling Pathways, Current Molecular Medicine 2014; 14 (5) . https://dx.doi.org/10.2174/1566524014666140603102459
DOI https://dx.doi.org/10.2174/1566524014666140603102459 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
- 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
-
Lactoferrin Derived Peptides: Mechanisms of Action and their Perspectives as Antimicrobial and Antitumoral Agents
Mini-Reviews in Medicinal Chemistry Regulation of Tumor Immune Microenvironment by Sphingolipids and Lysophosphatidic Acid
Current Drug Targets Targeting the Epidermal Growth Factor Receptor in Glioblastoma Treatment
Current Signal Transduction Therapy Genetic and Epigenetic Studies for Determining Molecular Targets of Natural Product Anticancer Agents
Current Cancer Drug Targets Modular Nanotransporters for Targeted Intracellular Delivery of Drugs: Folate Receptors as Potential Targets
Current Pharmaceutical Design GLP-1 Agonists Exenatide and Liraglutide: A Review About Their Safety and Efficacy
Current Clinical Pharmacology Development and Engineering of Lymphatic Endothelial Cells: Clinical Implications
Current Pharmaceutical Design Oral Inflammation and Bacteremia: Implications for Chronic and Acute Systemic Diseases Involving Major Organs
Cardiovascular & Hematological Disorders-Drug Targets Ototoxicity: Mechanisms of Cochlear Impairment and its Prevention
Current Medicinal Chemistry Phenolic Compounds in Prevention and Treatment of Skin Cancers: A Review
Current Medicinal Chemistry Patent Selections
Recent Patents on Anti-Cancer Drug Discovery Percutaneous Dilatational Tracheostomy - An Update
Current Respiratory Medicine Reviews Recent Advances of Kinesin Motor Inhibitors and their Clinical Progress
Reviews on Recent Clinical Trials Anti-cancer Drug Delivery Using Metal Organic Frameworks (MOFs)
Current Medicinal Chemistry Nanotechnology and Animal Health
Pharmaceutical Nanotechnology Antiviral Medication in Sexually Transmitted Diseases. Part I: HSV, HPV
Mini-Reviews in Medicinal Chemistry Role of Metabolic Enzymes P450 (CYP) on Activating Procarcinogen and their Polymorphisms on the Risk of Cancers
Current Drug Metabolism Human Saliva Metabolome for Oral Lichen Planus Biomarker Identification
Recent Patents on Anti-Cancer Drug Discovery Mechanisms of Resistance to Photodynamic Therapy
Current Medicinal Chemistry Is Src a Viable Target for Treating Solid Tumours?
Current Cancer Drug Targets