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Cucurbitacin B Induces DNA Damage, G2/M Phase Arrest, and Apoptosis Mediated by Reactive Oxygen Species (ROS) in Leukemia K562 Cells
- Source :
- Scopus-Elsevier
- Publication Year :
- 2014
- Publisher :
- Bentham Science Publishers Ltd., 2014.
-
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.
- Subjects :
- Cancer Research
Cell Survival
DNA damage
Antineoplastic Agents
Apoptosis
DNA Fragmentation
Flow cytometry
Histones
medicine
Humans
Viability assay
Cell Proliferation
Membrane Potential, Mitochondrial
Pharmacology
chemistry.chemical_classification
Reactive oxygen species
medicine.diagnostic_test
Chemistry
Free Radical Scavengers
Molecular biology
Triterpenes
Acetylcysteine
G2 Phase Cell Cycle Checkpoints
Comet assay
Biochemistry
Molecular Medicine
DNA fragmentation
Calcium
K562 Cells
Reactive Oxygen Species
K562 cells
Subjects
Details
- ISSN :
- 18715206
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Anti-Cancer Agents in Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....c7e723633f7a1da2760702d2b6e72fa5