Sulforaphane generates reactive oxygen species leading to mitochondrial perturbation for apoptosis in human leukemia U937 cells.
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.
Choi
Woo Young
WY
Department of Biology, College of Natural Sciences, Graduate School of Oriental Medicine, Pusan National University, Pusan 609-735, South Korea.
Choi
Byung Tae
BT
Lee
Won Ho
WH
Choi
Yung Hyun
YH
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004789:Enzyme Activation; D006801:Humans; D017879:Isothiocyanates; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D020298:U937 Cells
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013454:Sulfoxides; D013861:Thiocyanates; D053148:Caspase 3; C016766:sulforaphane