title: NecroX-5 prevents breast cancer metastasis by AKT inhibition via reducing intracellular calcium levels.
abstract: A major goal of breast cancer research is to prevent the molecular events that lead to tumour metastasis. It is well-established that both cytoplasmic and mitochondrial reactive oxygen species (ROS) play important roles in cell migration and metastasis. Accordingly, this study examined the molecular mechanisms of the anti-metastatic effects of NecroX-5, a mitochondrial ROS scavenger. NecroX-5 inhibited lung cancer metastasis by ameliorating migration in a mouse model. In human cancer cells, the inhibition of migration by NecroX-5 is cell type-dependent. We observed that the effect of NecroX-5 correlated with a reduction in mitochondrial ROS, but mitochondrial ROS reduction by MitoQ did not inhibit cell migration. NecroX-5 decreased intracellular calcium concentration by blocking Ca2+ influx, which mediated the inhibition of cell migration, AKT downregulation and the reduction of mitochondrial ROS levels. However, the reduction of mitochondrial ROS was not associated with supressed migration and AKT downregulation. Our study demonstrates the potential of NecroX-5 as an inhibitor of breast cancer metastasis.
authors.affiliation: Department of Microbiology and Immunology, INJE University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Physiology, INJE University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, INJE University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, INJE University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Ki Hyang
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Pathology, INJE University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Mi Seon
authors.initials: MS
authors.lastname: Kang
authors.affiliation: Graduate School, Department of Preventive Medicine, Kosin University College of Medicine, Busan 602-702, Republic of Korea.
authors.forename: Jun Hyuk
authors.initials: JH
authors.lastname: Hong
authors.affiliation: LG Life Science, Ltd., R&D Park, Daejeon 305-380, Republic of Korea.
authors.forename: Byeng Chul
authors.initials: BC
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, INJE University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Sungjae
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Microbiology and Immunology, INJE University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Su-Kil
authors.initials: SK
authors.lastname: Seo
authors.affiliation: Department of Microbiology and Immunology, INJE University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Il Whan
authors.initials: IW
authors.lastname: Choi
authors.affiliation: LG Life Science, Ltd., R&D Park, Daejeon 305-380, Republic of Korea.
authors.forename: Soon Ha
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Physiology, INJE University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Physiology, INJE University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Microbiology and Immunology, INJE University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Sae Gwang
authors.initials: SG
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage*; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D051058:Oncogene Protein v-akt / Q000096:biosynthesis* / Q000235:genetics; D009943:Organophosphorus Compounds / Q000008:administration & dosage; D017382:Reactive Oxygen Species / Q000378:metabolism; D013450:Sulfones / Q000008:administration & dosage*; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives; D023041:Xenograft Model Antitumor Assays
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; C574766:NecroX-5; D009943:Organophosphorus Compounds; D017382:Reactive Oxygen Species; D013450:Sulfones; D014451:Ubiquinone; C429014:mitoquinone; D051058:Oncogene Protein v-akt; D002118:Calcium