title: Juglone, from Juglans mandshruica Maxim, inhibits growth and induces apoptosis in human leukemia cell HL-60 through a reactive oxygen species-dependent mechanism.
abstract: Juglone, a major chemical constituent of Juglans mandshruica Maxim, is a promising anticancer agent that has shown a strong activity against cancer cells in vitro. Our previous study showed that juglone inhibited the proliferation of HL-60 cells with an IC50 value ∼8 μM. To further explore the proapoptotic mechanism of juglone, we investigated the role of the reactive oxygen species (ROS) in the apoptosis induced by juglone in HL-60 cells. The generation of ROS was about 2 to 8-fold as compared to control cell after treatment with juglone (2, 4 and 8 μM) for 24 h. The glutathione (GSH) depletion was consistent with ROS generation after treatment with juglone. Reversal of apoptosis in antioxidants (NAC and catalase) pretreated cells indicated the involvement of ROS in juglone-induced apoptosis. The cleavage of PARP and procaspase-3 and -9, loss of mitochondrial membrane potential (△Ψm), and release of cytochrome c (Cyt c) and Smac induced by juglone were significantly blocked by NAC. NAC also prevented the inhibition the phosphorylation of Akt and mTOR proteins by juglone. Collectively, these results indicated that ROS played a significant role in the apoptosis induced by juglone in human leukemia cell HL-60.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, and Department of Infectious Diseases, First Hospital, Changchun, PR China. xhl@jlu.edu.cn
authors.forename: Hua Li
authors.initials: HL
authors.lastname: Xu
authors.forename: Xiao Feng
authors.initials: XF
authors.lastname: Yu
authors.forename: Shao Chun
authors.initials: SC
authors.lastname: Qu
authors.forename: Xiang Ru
authors.initials: XR
authors.lastname: Qu
authors.forename: Yan Fang
authors.initials: YF
authors.lastname: Jiang
authors.forename: Da Yuan
authors.initials: da Y
authors.lastname: Sui
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017304:Annexin A5 / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D031324:Juglans / Q000737:chemistry*; D007938:Leukemia / Q000473:pathology*; D008564:Membrane Potentials / Q000187:drug effects; D009285:Naphthoquinones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D000975:Antioxidants; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D020169:Caspases; D005978:Glutathione; C005134:juglone; D000111:Acetylcysteine