title: Cholesterol oxidase from Bordetella species promotes irreversible cell apoptosis in lung adenocarcinoma by cholesterol oxidation.
abstract: Cholesterol oxidase (COD), an enzyme catalyzing the oxidation of cholesterol, has been applied to track the distribution of membrane cholesterol. Little investigations about the effect of COD on tumor cells have been performed. In the present study, we provided evidence that COD from Bordetella species (COD-B), induced apoptosis of lung cancer cells in vitro and in vivo. COD-B treatment inhibited Akt and ERK1/2 phosphorylation in dose- and time-dependent manner, which was not reversed and was even aggravated by cholesterol addition. Further investigation indicated that COD-B treatment promoted the generation of reactive oxygen species (ROS) and that cholesterol addition further elevated ROS levels. Moreover, COD-B treatment resulted in JNK and p38 phosphorylation, downregulation of Bcl-2, upregulation of Bax, activated caspase-3 and cytochrome C release, which likely responded to freshly produced hydrogen peroxide that accompanied cholesterol oxidation. Catalase pretreatment could only partially prevent COD-B-induced events, suggesting that catalase inhibited H2O2-induced signal transduction but had little effect on signal pathways involved in cholesterol depletion. Our results demonstrated that COD-B led to irreversible cell apoptosis by decreasing cholesterol content and increasing ROS level. In addition, COD-B may be a promising candidate for a novel anti-tumor therapy.
authors.affiliation: Department of General Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: G
authors.initials: G
authors.lastname: Xian
authors.affiliation: Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Obstetrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Obstetrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: H
authors.initials: H
authors.lastname: Lv
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province 250021, China.
authors.forename: S
authors.initials: S
authors.lastname: Xuan
authors.affiliation: Department of Center Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lin
authors.affiliation: 1] Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province 250021, China [2] Department of Center Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: L
authors.initials: L
authors.lastname: Gao
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D001884:Bordetella / Q000201:enzymology*; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D002789:Cholesterol Oxidase / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010084:Oxidation-Reduction; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001426:Bacterial Proteins; D017382:Reactive Oxygen Species; D002784:Cholesterol; D006861:Hydrogen Peroxide; D002789:Cholesterol Oxidase; D002374:Catalase; D053148:Caspase 3