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 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
-
MRI of Focal Liver Lesions
Current Medical Imaging The Challenges of Modeling Drug Resistance to Antiangiogenic Therapy
Current Drug Targets Pharmacological Profile and Pharmacogenomics of Anti-Cancer Drugs Used for Targeted Therapy
Current Cancer Drug Targets QSAR and Molecular Docking Techniques for the Discovery of Potent Monoamine Oxidase B Inhibitors: Computer-Aided Generation of New Rasagiline Bioisosteres
Current Topics in Medicinal Chemistry Microsomal Prostaglandin E Synthase: A Key Enzyme in PGE2 Biosynthesis and Inflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Inhibition of RET Activated Pathways: Novel Strategies for Therapeutic Intervention in Human Cancers
Current Pharmaceutical Design Patent Selections
Recent Patents on Anti-Cancer Drug Discovery Pharmacokinetics-Pharmacology Disconnection of Herbal Medicines and its Potential Solutions with Cellular Pharmacokinetic-Pharmacodynamic Strategy
Current Drug Metabolism Metabolomics as a Functional Tool in Screening Gastro Intestinal Diseases: Where are we in High Throughput Screening?
Combinatorial Chemistry & High Throughput Screening Editorial [Hot Topic: Emerging Therapeutic Targets and Agents for Pancreatic Cancer Therapy (Guest Editor: Dr. Felix Ruckert)]
Anti-Cancer Agents in Medicinal Chemistry Patents Related to Cancer Stem Cell Research
Recent Patents on DNA & Gene Sequences Surface Markers of Cancer Stem Cells in Solid Tumors
Current Stem Cell Research & Therapy Impaired Autophagy Mediates Resistance to Low-Dose Metronomic Cyclophosphamide Chemotherapy
Clinical Cancer Drugs p53: Fighting Cancer
Current Cancer Drug Targets From TGF-β to Cancer Therapy
Current Drug Targets Application of Molecular Imaging Technologies in Antitumor Drug Development and Therapy
Current Pharmaceutical Design Platelet Biomarkers in Tumor Growth
Current Proteomics EHAI: Enhanced Human Microbe-Disease Association Identification
Current Protein & Peptide Science Inhibitory Smad7: Emerging Roles in Health and Disease
Current Molecular Pharmacology Ontologies of Drug Discovery and Design for Neurology, Cardiology and Oncology
Current Pharmaceutical Design