Cucurbitacin B Induces DNA Damage, G2/M Phase Arrest, and Apoptosis Mediated by Reactive Oxygen Species (ROS) in Leukemia K562 Cells

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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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



Anti-Cancer Agents in Medicinal Chemistry, 14(8): 1146-1153.

Author(s): Jiajie Guo, Wenwen Zhao, Wenhui Hao, Guowen Ren, Jinjian Lu and Xiuping Chen.

Affiliation: Institute of Chinese Medical Sciences, University of Macau, Av. Padre Tomas Pereira S.J., Taipa, Macau, China.

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.



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Article Details

Volume: 14
Issue Number: 8
First Page: 1146
Last Page: 1153
Page Count: 8
DOI: 10.2174/1871520614666140601220915
Price: $58
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