The new isothiocyanate 4-(methylthio)butylisothiocyanate selectively affects cell-cycle progression and apoptosis induction of human leukemia cells.

Abstract

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.

• Authors: Carmela Fimognari, Michael Nüsse, Renato Iori, Giorgio Cantelli-Forti, Patrizia Hrelia
• Journal: Investigational new drugs (Invest New Drugs) Vol. 22 Issue 2 Pg. 119-29 (Apr 2004) ISSN: 0167-6997 [Print] United States
• PMID: 14739660 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-(methylthio)-3-butenyl isothiocyanate
• Isothiocyanates

Topics

• Apoptosis (drug effects, physiology)
• Cell Cycle (drug effects, physiology)
• Dose-Response Relationship, Drug
• Humans
• Isothiocyanates (chemistry, pharmacology)
• Jurkat Cells
• T-Lymphocytes (cytology, drug effects)