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