title: Induction of reactive oxygen species-mediated apoptosis by purified Schisandrae semen essential oil in human leukemia U937 cells through activation of the caspase cascades and nuclear relocation of mitochondrial apoptogenic factors.
abstract: The aim of this study was to evaluate the beneficial effects of Schisandrae semen essential oil (SSeo) on apoptosis events and the mechanisms associated with these effects in human leukemia U937 cells. The treatment of U937 cells with SSeo significantly inhibited survival and induced apoptosis. Schisandrae semen essential oil treatment increased the levels of death receptors and Fas, and activated caspases accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase, which was associated with the downregulation of members of the inhibitor of apoptosis protein family protein expression; however, a pan-caspase inhibitor reversed SSeo-induced apoptosis. Treating the cells with SSeo also caused truncation of Bid, translocation of proapoptotic Bax to the mitochondria, and loss of mitochondrial membrane permeabilization, thereby inducing the release of cytochrome c into the cytosol. Subsequently, SSeo upregulated the translocation of mitochondrial apoptogenic factors, such as endonuclease G and apoptosis-inducing factor, into the nucleus during the apoptotic process. Notably, SSeo immediately increased the generation of intracellular reactive oxygen species (ROS); however, pretreatment with N-acetylcysteine, a common ROS quencher, almost completely blocked SSeo-induced apoptosis. Taken together, these findings indicate that SSeo caused ROS- and caspase-dependent cell death involving mitochondrial dysfunction and nuclear translocation of mitochondrial proapoptosis proteins. Based on our data, the consumption of Schisandrae semen or its essential oil is a good natural therapeutic agent for anticancer activity and regression.
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan, 614-052, Republic of Korea.
authors.forename: Gyeong Jin
authors.initials: GJ
authors.lastname: Yu
authors.affiliation: Department of Microbiology, College of Medicine, Inje University, Busan, 608-737, Republic of Korea.
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju, 690-756, Republic of Korea.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Anti-Aging Research Center & Blue-Bio Industry Regional Innovation Center, Dongeui University, Busan, 614-714, Republic of Korea; Department of Food and Nutrition, College of Natural Sciences & Human Ecology, Dongeui University, Busan, 614-714, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.affiliation: Anti-Aging Research Center & Blue-Bio Industry Regional Innovation Center, Dongeui University, Busan, 614-714, Republic of Korea; Department of Life Science and Biotechnology, College of Natural Sciences & Human Ecology, Dongeui University, Busan, 614-714, Republic of Korea.
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Busan National University College of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Kim
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, 362-763, Republic of Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, 602-714, Republic of Korea. Electronic address: yhyoo@dau.ac.kr.
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan, 614-052, Republic of Korea; Anti-Aging Research Center & Blue-Bio Industry Regional Innovation Center, Dongeui University, Busan, 614-714, Republic of Korea. Electronic address: choiyh@deu.ac.kr.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000737:chemistry*; D009822:Oils, Volatile / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D032141:Schisandra / Q000737:chemistry*; D020298:U937 Cells; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D009822:Oils, Volatile; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D020169:Caspases; D000111:Acetylcysteine
keywords: AIF/EndoG; Apoptosis; Caspase; ROS; Schisandrae semen essential oil