Induction of apoptosis in murine lymphoma cells by cyclosporin A.
The aim of this study was to investigate if CsA could induce apoptosis in the murine T-lymphoma cell line LBC, whose growth is inhibited by this immunosuppressive drug. CsA induced programmed cell death in LBC cells with typical features of apoptosis demonstrated by exposure of phosphatidyl serine residues on the cell membrane, the decrease of cell DNA content, chromatin condensation, and nuclear fragmentation. Apoptosis was evident within 12 h after CsA incubation, with a maximal effect at 48 h, in a time and dose-dependent fashion. In addition, the role of apoptosis inhibitors (Bcl-2 and Bcl-x) and the apoptosis inducer (Bax) in CsA induced-apoptosis was evaluated. The expression of Bcl-2 and Bax proteins were high in LBC cells and following CsA treatment the expression of these proteins as well as Bcl-XL decreased. In this work we demonstrated that cell growth inhibition following CsA treatment in LBC was paralleled by the induction of apoptosis thus providing an interesting animal model to identify the mechanism participating in the regulation of apoptotic genes by CsA in T-cell neoplasms and to assess preclinical in vivo trials of T-cell lymphoma-related disorders.
Instituto de Estudios de la Inmunidad Humoral, IDEHU, UBA-CONICET, Catedra de Inmunologia, Facultad de Farmacia y Bioquimica, Buenos Aires 1113, Argentina.
C
C
Mongini
C
C
Waldner
E C
EC
Lopes
M J
MJ
Gravisaco
A
A
Escalada
M S
MS
Lockhart
E
E
Alvarez
S
S
Hajos
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016399:Lymphoma, T-Cell / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine