Fimognari Carmela, Nüsse Michael, Iori Renato, Cantelli-Forti Giorgio, Hrelia Patrizia
Department of Pharmacology, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.
Invest New Drugs. 2004 Apr;22(2):119-29. doi: 10.1023/B:DRUG.0000011788.19754.54.
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.
我们研究了新型异硫氰酸酯4-(甲硫基)丁基异硫氰酸酯(MTBITC)对Jurkat T白血病细胞增殖和凋亡的诱导作用。为了阐明MTBITC的作用是否对癌细胞具有特异性，我们对新鲜分离的、未转化的人外周血T淋巴细胞进行了MTBITC测试。MTBITC的作用具有白血病细胞特异性，包括细胞周期控制关键点(G2/M期转换)的紊乱。事实上，处理24小时后，G2期细胞比例明显增加(从约18%增至50%)，同时细胞周期蛋白B1的蛋白表达下降。MTBITC对细胞周期蛋白依赖性激酶(CDK)1表达的抑制作用较弱。我们的结果表明，高浓度的MTBITC还可通过增加p53和bax而非bcl-2的蛋白表达来诱导凋亡。MTBITC对未转化的T淋巴细胞无作用。考虑到其体外抗肿瘤活性和对白血病细胞的选择性，MTBITC可被视为癌症治疗中一种具有概念性前景的药物。
