Sulforaphane modulates cell cycle and apoptosis in transformed and non-transformed human T lymphocytes
Sulforaphane modulates cell cycle and apoptosis in transformed and non-transformed human T lymphocytes
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DOI：
10.1196/annals.1299.072
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发表时间：
2003-01-01
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影响因子：
--
通讯作者：
Hrelia, P
中科院分区：
文献类型：
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作者：
Fimognari, C;Nüsse, M;Hrelia, P
异硫氰酸酯对化学诱导的动物肿瘤发挥化学预防作用，调节致癌物活化/解毒和/或诱导肿瘤细胞系中细胞周期停滞和凋亡所需的酶。为了探讨异硫氰酸酯的化学预防潜力，我们研究了异硫氰酸酯萝卜硫素对Jurkat T-白血病细胞增殖、凋亡诱导以及p53、bcl-2和bax蛋白表达的影响。莱菔硫烷可引起G2/M期延迟和凋亡细胞比例增加，并呈时间和剂量依赖性。在长时间暴露于高剂量的萝卜硫素后观察到坏死。p53、bax蛋白表达明显增加，bcl-2蛋白表达无明显变化。由于对正常宿主组织的选择性靶向和低毒性是所提出的化学预防剂如萝卜硫素的基本前提，我们在非转化的植物血凝素刺激的人T淋巴细胞上测试了萝卜硫素。我们证明了萝卜硫素通过显著下调细胞周期蛋白D3而将细胞周期进程阻滞在G期。此外，萝卜硫素诱导细胞凋亡（也坏死），介导的p53的表达增加，而它对bcl-2和bax的水平几乎没有影响。这些发现表明萝卜硫素可以发挥抑制白血病细胞生长的保护作用。此外，萝卜硫素不仅在转化的淋巴细胞中，而且在它们的正常对应物中也是活性的。虽然体外研究不一定能预测体内结果，但我们的研究结果提出了关于萝卜硫素用于癌症化学预防的适用性的重要问题。
Isothiocyanates exert chemopreventive effects against chemically induced tumors in animals, modulating enzymes required for carcinogens' activation/detoxification and/or the induction of cell-cycle arrest and apoptosis in tumor cell lines. To investigate the chemopreventive potential of isothiocyanates, we studied proliferation, apoptosis induction and p53, bcl-2 and bax protein expression in Jurkat T-leukemia cells by the isothiocyanate sulforaphane. Sulforaphane caused G(2)/M-Phase delay and increase of apoptotic cell fraction in a time- and dose-dependent manner. Necrosis was observed after prolonged exposure to elevated sulforaphane doses. Moreover, it markedly increased p53 and bax protein expression, and slightly affected bcl-2 expression. Since selective targeting and low toxicity for normal host tissues are fundamental requisites for proposed chemopreventive agents,such as sulforaphane, we tested sulforaphane on non-transformed phytohemagglutinin-stimulated human T-lymphocytes. We demonstrated that sulforaphane arrested cell-cycle progression in G, phase by a significant down-modulation of cyclin D3. Moreover, sulforaphane induced apoptosis (and also necrosis), mediated by an increase in the expression of p53, whereas it exerted little effect on bcl-2 and bax levels. These findings indicate that sulforaphane can exert protective effects inhibiting leukemic cell growth. Moreover, sulforaphane is active not only in transformed lymphocytes but also in their normal counterpart. Although in vitro studies do not necessarily predict in vivo outcomes, our findings raise important questions regarding the suitability of sulforaphane for cancer chemoprevention.