The new isothiocyanate 4-(methylthio)butylisothiocyanate selectively affects cell-cycle progression and apoptosis induction of human leukemia cells.
We investigated proliferation and apoptosis induction in Jurkat T-leukemia cells by the new isothiocyanate 4-(methylthio)butylisothiocyanate (MTBITC). To help elucidate whether the effects of MTBITC are specific for cancer cells, we tested MTBITC on freshly isolated, non-transformed human peripheral T lymphocytes. The effects of MTBITC are leukemic-cell-specific and consist of derangements in a critical point of cell-cycle control (G2/M transition). In fact, an increase in the proportion of G2 cells (from about 18% to 50%) was apparent following 24 h of treatment, associated with a decrease in the protein expression of cyclin B1. The expression of cyclin-dependent kinase (CDK) 1 was more mildly attenuated by MTBITC. Our results demonstrated that high concentrations of MTBITC can also induce apoptosis, through an increase of p53 and bax, but not bcl-2, protein expression. No effects of MTBITC were demonstrated on non-transformed T lymphocytes. Taking into account its in vitro antineoplastic activity and selectivity toward leukemia cells, MTBITC can be viewed as a conceptually promising agent in cancer therapy.
Fimognari
Carmela
C
Department of Pharmacology, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.
Nüsse
Michael
M
Iori
Renato
R
Cantelli-Forti
Giorgio
G
Hrelia
Patrizia
P
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry / Q000494:pharmacology*; D019169:Jurkat Cells; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
C447639:4-(methylthio)-3-butenyl isothiocyanate; D017879:Isothiocyanates