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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
Guo J.; Zhao W.; Hao W.; Ren G.; Lu J.; Chen X.
2014-09-01
Source PublicationAnti-Cancer Agents in Medicinal Chemistry
ISSN18755992 18715206
Volume14Issue:8Pages:1146-1153
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.

KeywordApoptosis Cancer Cucurbitacin b Dna Damage G2/m Arrest Ros
DOI10.2174/1871520614666140601220915
URLView the original
Indexed BySCI
WOS Research AreaOncology ; Pharmacology & Pharmacy
WOS SubjectOncology ; Chemistry, Medicinal
WOS IDWOS:000341885400011
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被引频次[WOS]:22   [WOS记录]     [WOS相关记录]
Document TypeJournal article
专题Institute of Chinese Medical Sciences
AffiliationUniversidade de Macau
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GB/T 7714
Guo J.,Zhao W.,Hao W.,et al. Cucurbitacin B induces DNA damage, G2/M phase arrest, and apoptosis mediated by reactive oxygen species (ROS) in leukemia K562 cells[J]. Anti-Cancer Agents in Medicinal Chemistry,2014,14(8):1146-1153.
APA Guo J.,Zhao W.,Hao W.,Ren G.,Lu J.,&Chen X..(2014).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.
MLA Guo J.,et al."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(2014):1146-1153.
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