Sulforaphane generates reactive oxygen species leading to mitochondrial perturbation for apoptosis in human leukemia U937 cells |
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Authors: | Woo Young Choi Byung Tae Choi Won Ho Lee Yung Hyun Choi |
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Institution: | 1. Department of Biology, College of Natural Sciences, Graduate School of Oriental Medicine, Pusan National University, Pusan 609-735, South Korea;2. Department of Anatomy, Graduate School of Oriental Medicine, Pusan National University, Pusan 609-735, South Korea;3. Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control, Dongeui University Graduate School, Busan 614-052, South Korea |
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Abstract: | Sulforaphane, an isothiocyanate found in cruciferous vegetables, has been shown to possess growth-inhibiting and apoptosis-inducing activities in cancer cell lines in vitro. In order to further explore the critical events leading to apoptosis in sulforaphane-treated U937 human leukemia cells, the following effects of sulforaphane on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS), alteration of the mitochondrial membrane potential (MMP), and the expression changes of Bcl-2 family proteins. The cytotoxic effect of sulforaphane was mediated by its induction of apoptosis as characterized by the occurrence of DNA ladders, apoptotic bodies and chromosome condensation in U937 cells. The sulforaphane-induced apoptosis in U937 cells correlated with the generation of intracellular ROS, collapse of MMP, activation of caspase-3, and down-regulation of anti-apoptotic Bcl-2 expression. The quenching of ROS generation with antioxidant N-acetyl-l-cysteine conferred significant protection against sulforaphane-elicited ROS generation, disruption of the MMP, caspase-3 activation and apoptosis. In conclusion, the present study reveals that the cellular ROS generation plays a pivotal role in the initiation of sulforaphane-triggered apoptotic death in U937 cells. |
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Keywords: | Sulforaphane Apoptosis Reactive oxygen species Mitochondrial membrane potential |
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