title: Antibody ligation of CM1 on cisplatin-exposed HeLa cells induces apoptosis through reactive oxygen species-dependent Fas ligand expression.
abstract: Centrocyte/centroblast marker 1 (CM1) has been identified as a pro-apoptosis molecule on B-cell lymphoma cells as well as several types of cancer cells. In this study, we investigated its signaling mechanism in HeLa cells after treatment with cisplatin in order to potentially identify a new therapeutic target. The CM1 molecule was induced on the surface of cisplatin-exposed HeLa cells. In these cells, ligation of CM1 with anti-CM1 monoclonal antibodies inhibited cell proliferation and produced reactive oxygen species. Fas ligand (FasL) expression was upregulated without upregulating Fas in cisplatin-exposed HeLa cells after CM1 stimulation. Pretreatment with N-acetylcysteine, a pan-capase inhibitor, and ZB4, an antagonistic anti-Fas antibody, effectively inhibited the apoptotic effect triggered by CM1. CM1 ligation induced apoptosis through disruption of the mitochondrial membrane potential, decreased Bcl-2 and phosphorylated ERK expression. These findings identify CM1 as a potential new therapeutic target related to cisplatin-exposed cervical cancer.
authors.affiliation: Department of Anatomy and Research Center for Woman Disease, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Ga Bin
authors.initials: GB
authors.lastname: Park
authors.affiliation: Department of Anatomy and Research Center for Woman Disease, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Daejin
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Research Center for Woman Disease, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Hoi Soo
authors.initials: HS
authors.lastname: Yoon
authors.affiliation: Department of Anatomy and Research Center for Woman Disease, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Yeong-Seok
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
authors.forename: Ki Tae
authors.initials: KT
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
authors.forename: Dae Hoon
authors.initials: DH
authors.lastname: Jeong
authors.affiliation: Department of Obstetrics and Gynecology, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Hur
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D049109:Cell Proliferation / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D053222:Fas Ligand Protein / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells / Q000187:drug effects*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019014:fas Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; C491901:FAS protein, human; D053222:Fas Ligand Protein; D017382:Reactive Oxygen Species; C585430:centrocyte centroblast marker 1 protein, human; D019014:fas Receptor; D002945:Cisplatin; D000111:Acetylcysteine