Abstract
To search for new chemotherapeutic agents to treat colorectal cancer, we isolated a number of natural ent-kaurane diterpenoids from the plant Croton tonkinensis. Among them, only CeKDs with the 15-oxo-16-ene moiety induced the apoptosis of colorectal cancer cell lines Caco-2 and LS180. The active CeKD induced the activation of ERK and JNK, but the inactive ones induced that of ERK, but not that of JNK. It thus appears that JNK seemed to play an important role in the apoptotic activity of the active compounds. The dualspecificity JNK kinase MKK4 was activated in both colorectal cancer cells treated with the active CeKD, but MKK7 was not activated. Further, the active CeKD, but not the inactive one, enhanced the generation of intracellular reactive oxygen species (ROS) in both cells. CeKD-induced cell apoptosis and ROS generation, as well as JNK activation, were inhibited by the antioxidant N-acetyl-L-cysteine. These findings suggest that ROS stimulated the phosphorylation of JNK mediated by MKK4 and played a critical role in CeKD-induced apoptosis in colorectal cancer cells.
Keywords: Apoptosis, Colon cancer, Croton ent-kaurane diterpenoid, JNK, 15-oxo-16-ene, Reactive oxygen species (ROS).
Anti-Cancer Agents in Medicinal Chemistry
Title:ent-Kaurane Diterpenoids from Croton tonkinensis Induce Apoptosis in Colorectal Cancer Cells through the Phosphorylation of JNK Mediated by Reactive Oxygen Species and Dual-Specificity JNK Kinase MKK4
Volume: 14 Issue: 7
Author(s): Phuong Thien Thuong, Nguyen Minh Khoi, Saho Ohta, Shinichiro Shiota, Hironori Kanta, Kenji Takeuchi and Fumiaki Ito
Affiliation:
Keywords: Apoptosis, Colon cancer, Croton ent-kaurane diterpenoid, JNK, 15-oxo-16-ene, Reactive oxygen species (ROS).
Abstract: To search for new chemotherapeutic agents to treat colorectal cancer, we isolated a number of natural ent-kaurane diterpenoids from the plant Croton tonkinensis. Among them, only CeKDs with the 15-oxo-16-ene moiety induced the apoptosis of colorectal cancer cell lines Caco-2 and LS180. The active CeKD induced the activation of ERK and JNK, but the inactive ones induced that of ERK, but not that of JNK. It thus appears that JNK seemed to play an important role in the apoptotic activity of the active compounds. The dualspecificity JNK kinase MKK4 was activated in both colorectal cancer cells treated with the active CeKD, but MKK7 was not activated. Further, the active CeKD, but not the inactive one, enhanced the generation of intracellular reactive oxygen species (ROS) in both cells. CeKD-induced cell apoptosis and ROS generation, as well as JNK activation, were inhibited by the antioxidant N-acetyl-L-cysteine. These findings suggest that ROS stimulated the phosphorylation of JNK mediated by MKK4 and played a critical role in CeKD-induced apoptosis in colorectal cancer cells.
Export Options
About this article
Cite this article as:
Thuong Thien Phuong, Khoi Minh Nguyen, Ohta Saho, Shiota Shinichiro, Kanta Hironori, Takeuchi Kenji and Ito Fumiaki, ent-Kaurane Diterpenoids from Croton tonkinensis Induce Apoptosis in Colorectal Cancer Cells through the Phosphorylation of JNK Mediated by Reactive Oxygen Species and Dual-Specificity JNK Kinase MKK4, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (7) . https://dx.doi.org/10.2174/1871520614666140127111407
DOI https://dx.doi.org/10.2174/1871520614666140127111407 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
- 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
-
Nanomaterials in the Pharmaceuticals: Occurrence, Behaviour and Applications
Current Pharmaceutical Design Editorial (Thematic Issue: The Predictive Pathology in the Target Therapy Era)
Current Drug Targets Biomarkers to Assess the Targeting of DNA Repair Pathways to Augment Tumor Response to Therapy
Current Molecular Medicine Immunotoxicity, Flow Cytometry, and Chemoinformatics: Review, Bibliometric Analysis, and New QSAR Model of Drug Effects Over Macrophages
Current Topics in Medicinal Chemistry CCL2-CCR2 Signaling in Disease Pathogenesis
Endocrine, Metabolic & Immune Disorders - Drug Targets Oncolytic Viruses for Induction of Anti-Tumor Immunity
Current Pharmaceutical Biotechnology Subject Index To Volume 1
Recent Patents on Anti-Cancer Drug Discovery Targeting miRNAs for Pancreatic Cancer Therapy
Current Pharmaceutical Design Fatty Acid (FA) Compositions and Trans Content of Frequently Consumed Edible Oils and Fats from Iran’ Market
Current Nutrition & Food Science Combined Cancer Therapy with Non-Conventional Drugs: All Roads Lead to AMPK
Mini-Reviews in Medicinal Chemistry Anti-IL-12/23 in Crohn's Disease: Bench and Bedside
Current Drug Targets The Role of Tumor Suppressor Dysregulation in Prostate Cancer Progression
Current Drug Targets The Scatter Factor Signaling Pathways as Therapeutic Associated Target in Cancer Treatment
Current Medicinal Chemistry Bcl-2 Inhibitors: Emerging Drugs in Cancer Therapy
Current Medicinal Chemistry MicroRNA in Cervical Carcinogenesis: Window of Therapeutic Potential
Current Women`s Health Reviews Three Decades of P-gp Inhibitors: Skimming Through Several Generations and Scaffolds
Current Medicinal Chemistry The Optimal Treatment of Thyroid Gland Function Disturbances During Pregnancy
Current Pharmaceutical Biotechnology Targeting Angiogenesis for Treatment of NSCLC Brain Metastases
Current Cancer Drug Targets Natural-based Hydrogels: A Journey from Simple to Smart Networks for Medical Examination
Current Medicinal Chemistry Synthesis and Characterization of Two New Thiophene Acetyl Salicylic Acid Esters and their ortho- and para-effect on Anticancer Activity
Anti-Cancer Agents in Medicinal Chemistry