Quercetin inhibits lymphocyte activation and proliferation without inducing apoptosis in peripheral mononuclear cells
Quercetin inhibits lymphocyte activation and proliferation without inducing apoptosis in peripheral mononuclear cells
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DOI：
10.1016/j.leukres.2008.07.025
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发表时间：
2009-01-01
影响因子：
2.7
通讯作者：
Cossarizza, Andrea
中科院分区：
文献类型：
--
作者：
Lugli, Enrico;Ferraresi, Roberta;Cossarizza, Andrea
化疗药物对正常细胞的毒性是癌症治疗的严重副作用。因此，寻找对正常细胞低毒性的分子至关重要。几种天然化合物，例如类黄酮槲皮素，作为“化学预防剂”受到越来越多的关注。槲皮素可杀死肿瘤来源的细胞系，但对其对正常细胞的影响知之甚少。在这里，我们发现，虽然槲皮素对白血病细胞系比外周血单核细胞（PBMC）具有更高的凋亡潜力，并且不会使 PBMC 对 CD95 诱导的细胞凋亡敏感，但它能够抑制正常的免疫功能，例如 T 细胞增殖和激活。槲皮素敏感性与细胞周期进展无关，因为在血清饥饿的 U937 细胞中，槲皮素敏感性并未被消除，并且在槲皮素处理后，增殖的 PBMC 也不会发生凋亡。然而，槲皮素可阻止 PHA 诱导的 PBMC 增殖和 SEB 诱导的激活标记物上调。我们的数据表明，槲皮素虽然在多种条件下不能诱导正常细胞凋亡，但可能会干扰效应 T 细胞功能。 (C) 2008 Elsevier Ltd. 保留所有权利。
Toxicity of chemotherapeutic drugs towards normal cells is a serious side effect of cancer treatment. Thus, finding of molecules with low toxicity for normal cells is crucial. Several natural compounds, such as flavonoid quercertin, are receiving a growing attention as "chemopreventers". Quercetin kills tumour-derived cell lines, but little is known about its effects on normal cells. Here we show that although quercetin exerts a higher apoptotic potential on leukemic cell lines than on peripheral blood mononuclear cells (PBMCs) and does not sensitize PBMCs to CD95-induced apoptosis, it is able to inhibit normal immune functions such as T cell proliferation and activation. Quercetin sensitivity is independent on cell cycle progression since it was not abrogated in serum-starved U937 cells, nor proliferating PBMCs underwent apoptosis after quercetin treatment. However, quercetin prevented PHA-induced PBMC proliferation and SEB-induced upregulation of activation markers. Our data suggest that quercetin, while incapable of inducing apoptosis in normal cells under several conditions, could interfere with effector T cell function. (C) 2008 Elsevier Ltd. All rights reserved.