Cisplatin augments FAS-mediated apoptosis through lipid rafts.
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.
Huang
Cheng-Ri
CR
Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan.
Jin
Zhe-Xiong
ZX
Dong
Lingli
L
Tong
Xiao-Peng
XP
Yue
Sun
S
Kawanami
Takafumi
T
Sawaki
Toshioki
T
Sakai
Tomoyuki
T
Miki
Miyuki
M
Iwao
Haruka
H
Nakajima
Akio
A
Masaki
Yasufumi
Y
Fukushima
Yoshihiko
Y
Tanaka
Masao
M
Fujita
Yoshimasa
Y
Nakajima
Hideo
H
Okazaki
Toshiro
T
Umehara
Hisanori
H
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*
D000970:Antineoplastic Agents; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D019014:fas Receptor; D053148:Caspase 3; D053181:Caspase 8; D002945:Cisplatin