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
-
The mAP-KL Algorithm Combined with Mutual Information Network Used to Screen Hub Genes in Osteosarcoma
Current Bioinformatics Non-Viral Gene Delivery Methods
Current Pharmaceutical Biotechnology Dietary Manipulation of Precursor Polyunsaturated Fatty Acids Modulates Eicosanoid and Endocannabinoid Synthesis: A Potential Tool to Control Tumor Development
Current Nutrition & Food Science Can we Target the Chemokine Network for Cancer Therapeutics?
Current Cancer Drug Targets Bone Modulating Bioactive Natural Compounds: Review
Current Bioactive Compounds Characteristic Alterations of Nuclear Structure and Chromatin Organisation of Cancer Cells Addressed by Proteome Analysis**
Current Proteomics Applications of Nanosystems to Anticancer Drug Therapy (Part II. Dendrimers, Micelles, Lipid-based Nanosystems)
Recent Patents on Anti-Cancer Drug Discovery PACAP is Implicated in the Stress Axes
Current Pharmaceutical Design Bone Marrow Concentrate: A Novel Strategy for Bone Defect Treatment
Current Stem Cell Research & Therapy Natural Compounds with Proteasome Inhibitory Activity for Cancer Prevention and Treatment
Current Protein & Peptide Science Improved Drug Delivery System for Cancer Treatment by D-Glucose Conjugation with Eugenol From Natural Product
Current Drug Delivery Exosomal miR-214-5p Released from Glioblastoma Cells Modulates Inflammatory Response of Microglia after Lipopolysaccharide Stimulation through Targeting CXCR5
CNS & Neurological Disorders - Drug Targets Eph/Ephrin Signalling and Function in Oncogenesis: Lessons from Embryonic Development
Current Cancer Drug Targets The Role of Anionic Polysaccharides in the Preparation of Nanomedicines with Anticancer Applications
Current Pharmaceutical Design Regulation of Angiogenesis by the Small Heat Shock Protein αB-Crystallin
Current Angiogenesis (Discontinued) Evidence for Predominance of CCR5-Using HIV-1 Strains During Highly Active Antiretroviral Therapy
Current HIV Research Negative Regulation of NEDD8 Conjugation Pathway by Novel Molecules and Agents for Anticancer Therapy
Current Pharmaceutical Design Stem Cell-based Tissue Engineering Approaches for Musculoskeletal Regeneration
Current Pharmaceutical Design Recent Developments in the Field of Anticancer Platinum Complexes
Recent Patents on Anti-Cancer Drug Discovery The Synthesis of Nano-Doxorubicin and its Anticancer Effect
Anti-Cancer Agents in Medicinal Chemistry