Abstract
Cucurbitacin B (Cuc B) is a natural product with potent anti-cancer activities in solid tumors. We investigated the anti-cancer effect of Cuc B on K562 leukemia cells. Cuc B drastically decreased cell viability in a concentration-dependent manner. Cuc B treatment caused DNA damage, as shown by long tails in the comet assay and increased γH2AX protein expression. Immunofluorescence, Fluo3- AM, and JC-1 staining results showed that Cuc B treatment induced nuclear γH2AX foci, increased intracellular calcium ion concentration, and depolarized mitochondrial membrane potential (MMP), respectively. Cuc B induced G2/M phase arrest and apoptosis, as shown by flow cytometry, DNA fragmentation, and protein expression analyses. In addition, Cuc B dramatically increased intracellular reactive oxygen species (ROS) generation as measured by DCFH2-DA. N-acetyl-l-cysteine pretreatment significantly reversed Cuc B-induced DNA damage, increased intracellular calcium ion concentration, and reduced MMP, G2/M phase arrest, and apoptosis. Taken together, these results suggested that ROS mediated Cuc B-induced DNA damage, G2/M arrest, and apoptosis in K562 cells. This study provides novel mechanisms to better understand the underlying anti-cancer mechanisms of Cuc B.
Keywords: Apoptosis, cancer, cucurbitacin B, DNA damage, G2/M arrest, ROS.
Anti-Cancer Agents in Medicinal Chemistry
Title:Cucurbitacin B Induces DNA Damage, G2/M Phase Arrest, and Apoptosis Mediated by Reactive Oxygen Species (ROS) in Leukemia K562 Cells
Volume: 14 Issue: 8
Author(s): Jiajie Guo, Wenwen Zhao, Wenhui Hao, Guowen Ren, Jinjian Lu and Xiuping Chen
Affiliation:
Keywords: Apoptosis, cancer, cucurbitacin B, DNA damage, G2/M arrest, ROS.
Abstract: Cucurbitacin B (Cuc B) is a natural product with potent anti-cancer activities in solid tumors. We investigated the anti-cancer effect of Cuc B on K562 leukemia cells. Cuc B drastically decreased cell viability in a concentration-dependent manner. Cuc B treatment caused DNA damage, as shown by long tails in the comet assay and increased γH2AX protein expression. Immunofluorescence, Fluo3- AM, and JC-1 staining results showed that Cuc B treatment induced nuclear γH2AX foci, increased intracellular calcium ion concentration, and depolarized mitochondrial membrane potential (MMP), respectively. Cuc B induced G2/M phase arrest and apoptosis, as shown by flow cytometry, DNA fragmentation, and protein expression analyses. In addition, Cuc B dramatically increased intracellular reactive oxygen species (ROS) generation as measured by DCFH2-DA. N-acetyl-l-cysteine pretreatment significantly reversed Cuc B-induced DNA damage, increased intracellular calcium ion concentration, and reduced MMP, G2/M phase arrest, and apoptosis. Taken together, these results suggested that ROS mediated Cuc B-induced DNA damage, G2/M arrest, and apoptosis in K562 cells. This study provides novel mechanisms to better understand the underlying anti-cancer mechanisms of Cuc B.
Export Options
About this article
Cite this article as:
Guo Jiajie, Zhao Wenwen, Hao Wenhui, Ren Guowen, Lu Jinjian and Chen Xiuping, Cucurbitacin B Induces DNA Damage, G2/M Phase Arrest, and Apoptosis Mediated by Reactive Oxygen Species (ROS) in Leukemia K562 Cells, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (8) . https://dx.doi.org/10.2174/1871520614666140601220915
DOI https://dx.doi.org/10.2174/1871520614666140601220915 |
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
-
Development of Patents and Clinical Trials on Regenerative Therapy: Gene Therapy
Recent Patents on Regenerative Medicine Vitamin D and Physical Performance in Athletes
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Therapeutic Applications of Crocus sativus L. (Saffron): A Review
The Natural Products Journal Radium-223: From Radiochemical Development to Clinical Applications in Targeted Cancer Therapy
Current Radiopharmaceuticals Translational Research of Photodynamic Therapy with Acridine Orange which Targets Cancer Acidity
Current Pharmaceutical Design Stem Cell-Based Immunomodulation in Type 1 Diabetes: Beyond the Regenerative Approach
Current Pharmaceutical Design Hyaluronan/Hyaladherins - a Promising Axis for Targeted Drug Delivery in Cancer
Current Drug Delivery Recent Progress in the Development of Anticancer Agents
Current Medicinal Chemistry - Anti-Cancer Agents Bacteria and Bacterial Toxins as Therapeutic Agents for Solid Tumors
Current Cancer Drug Targets Cellular Changes, Molecular Pathways and the Immune System Following Photodynamic Treatment
Current Medicinal Chemistry Chemokines and Chemokine Receptors: Potential Therapeutic Targets in Multiple Sclerosis
Current Drug Targets - Inflammation & Allergy Down Regulation of Differentiated Embryo-Chondrocyte Expressed Gene 1 is Related to the Decrease of Osteogenic Capacity
Current Drug Targets Peptides for Tumour Therapy and Diagnosis: Current Status and Future Directions
Current Medicinal Chemistry The Urokinase Receptor in the Central Nervous System
CNS & Neurological Disorders - Drug Targets The Efficacy and Mechanism of Proteasome Inhibitors in Solid Tumor Treatment
Recent Patents on Anti-Cancer Drug Discovery Tumor Bone Diseases: Molecular Mechanisms and Opportunities for Novel Treatments
Current Medicinal Chemistry - Anti-Cancer Agents The Function of LncRNA FTX in Several Common Cancers
Current Pharmaceutical Design The Heat Shock Protein 90 Chaperone Complex: An Evolving Therapeutic Target
Current Cancer Drug Targets Purification and Characterization of a Lectin from the Indian Cultivar of French Bean Seeds
Protein & Peptide Letters Role of Wnt/β-catenin Signaling in Drug Resistance of Pancreatic Cancer
Current Pharmaceutical Design