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
-
Synthetic Peptide Libraries: From Random Mixtures to In Vivo Testing
Current Medicinal Chemistry Generation of Anti-Colorectal Cancer Fab Phage Display Libraries With a High Percentage of Diverse Antigen-Reactive Clones
Combinatorial Chemistry & High Throughput Screening Pharmacokinetics and Systems Pharmacology of Anti-CD47 Macrophage Immune Checkpoint Inhibitor Hu5F9-G4
Current Pharmacogenomics and Personalized Medicine Withdrawal Notice: Role, Significance and Association of microRNA-10a/b in Physiology of Cancer
MicroRNA NHE-1: A Promising Target for Novel Anti-cancer Therapeutics
Current Pharmaceutical Design Enhancing Endothelial Progenitor Cell Function Through Selective Estrogen Receptor Modulation: A Potential Approach to Cardiovascular Risk Reduction
Cardiovascular & Hematological Agents in Medicinal Chemistry Anti-VEGF Compounds in the Treatment of Neovascular Age Related Macular Degeneration
Current Drug Targets BCL-2 Family Proteins: The Mitochondrial Apoptotic Key Regulators
Current Cancer Therapy Reviews DNA Secondary Structure at Chromosomal Fragile Sites in Human Disease
Current Genomics Epigenetic Targeting of Platinum Resistant Testicular Cancer
Current Cancer Drug Targets Prospects for Plant-Derived Chemopreventive Agents Exhibiting Multiple Mechanisms of Action
Current Medicinal Chemistry - Anti-Cancer Agents Role of Lipid Rafts/Caveolae in the Anticancer Effect of Endocannabinoids
Mini-Reviews in Medicinal Chemistry Olive Oil and Apoptosis of Cancer Cells
Current Nutrition & Food Science Melanoma Immunotherapy: Past, Present, and Future
Current Pharmaceutical Design Targeting the BRCA1/2 Tumor Suppressors
Current Drug Targets Current Drug Design of Anti-HIV Agents Through the Inhibition of C-C Chemokine Receptor Type 5
Current Computer-Aided Drug Design Application of Machine Learning Approaches for Protein-protein Interactions Prediction
Medicinal Chemistry Neonatal Germ Cell Tumors
Current Pediatric Reviews Brain Tumour Stem Cells: Implications for Cancer Therapy and Regenerative Medicine
Current Stem Cell Research & Therapy The Relevance of Microdialysis for Clinical Oncology
Current Clinical Pharmacology