Differential effects of two isothiocyanates on cell cycle progression and apoptosis in human T-cell leukaemia and human lymphocytes

C Fimognari PhDa, M Nuesse PhDb, R Iori PhDc, G Cantelli-Forti PhDa, P Hrelia PhDa

aDepartment of Pharmacology, University of Bologna, Bologna, Italy, bGSF-Flow Cytometry Group, Muenchen, Germany, cIstituto Sperimentale per le Colture Industriali, MiPA, Bologna, Italy

AIM: We investigated proliferation and apoptosis induction in Jurkat T-leukemia cells by 4-(methylthio)butylisothiocyanate (MTBITC) and sulforaphane. To establish that the effects of the ITCs are cell-specific, we investigated whether proliferation and apoptosis are also altered by the ITCs in non transformed primary human lymphocytes. METHODS: Jurkat cells and lymphocytes were treated with different doses of MTBITC (1, 3 and 10 µg) or sulforaphane (3, 10 and 30 µg). Cell cycle progression, apoptosis, and p53, bax and bcl-2 protein levels were assessed by flow cytometry. Results were analysed by two-sided Fisher’s exact test and T test. RESULTS: The effects of MTBITC are neoplastic-cell-specific and consist of derangements in two critical points of cell cycle control (G1/S and G2/M transition) and subsequent apoptosis, associated with an increase of p53 and bax (P=0.0270 and P=0.0137, respectively), but not bcl-2, protein expression. Sulforaphane causes G2/M-phase arrest, increase of apoptotic cell fraction (P<0.0001), and p53 and bax protein expression both in Jurkat cells and in lymphocytes (P=0.003). CONCLUSIONS: The ITCs studied can be viewed as conceptually promising agents in cancer therapy. Taking into account the unique in vitro antitumor activity and selectivity toward cancer cells, MTBITC is an interesting chemotherapeutic antileukaemic agent. Further in-depth in vitro studies have to be performed for understanding the mechanisms responsible for the different activity of MTBITC and sulforaphane and for comparing their activity on different cell types. In vivo studies may then lead to clinical trials to investigate the therapeutic potential of two ITCs.

KEY WORDS: isothiocyanates, chemoprevention, cell cycle, apoptosis.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Apoptosis - Molecular Mechanisms.