title: Cisplatin augments FAS-mediated apoptosis through lipid rafts.
abstract: Cisplatin is widely and effectively used for the treatment of various types of cancer. However, its biochemical mechanisms are still unelucidated. Previously, we reported that membrane sphingomyelin (SM) was important for FAS-mediated apoptosis through lipid raft function. In this study, we strikingly show that cisplatin combined with CH11 (anti-FAS antibody, IgM) was able to induce marked apoptosis in SM synthase-restored WR/Fas-SMS1 cells, but not in SM synthase-deficient WR/FAS-SM(-) cells. In addition, we demonstrated that membrane SM played an important role in cisplatin/CH11-induced apoptosis through the classical caspase-dependent pathway, mainly by enhancing the formation of FAS-associated signaling complexes.
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan.
authors.forename: Cheng-Ri
authors.initials: CR
authors.lastname: Huang
authors.forename: Zhe-Xiong
authors.initials: ZX
authors.lastname: Jin
authors.forename: Lingli
authors.initials: L
authors.lastname: Dong
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Tong
authors.forename: Sun
authors.initials: S
authors.lastname: Yue
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kawanami
authors.forename: Toshioki
authors.initials: T
authors.lastname: Sawaki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Sakai
authors.forename: Miyuki
authors.initials: M
authors.lastname: Miki
authors.forename: Haruka
authors.initials: H
authors.lastname: Iwao
authors.forename: Akio
authors.initials: A
authors.lastname: Nakajima
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Masaki
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Fujita
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakajima
authors.forename: Toshiro
authors.initials: T
authors.lastname: Okazaki
authors.forename: Hisanori
authors.initials: H
authors.lastname: Umehara
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000032:analysis; D053181:Caspase 8 / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D053200:Fas-Associated Death Domain Protein / Q000502:physiology; D006801:Humans; D021962:Membrane Microdomains / Q000187:drug effects* / Q000502:physiology; D019014:fas Receptor / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D019014:fas Receptor; D053148:Caspase 3; D053181:Caspase 8; D002945:Cisplatin