Role of transglutaminase 2 in quercetin-induced differentiation of B16-F10 murine melanoma cells
Role of transglutaminase 2 in quercetin-induced differentiation of B16-F10 murine melanoma cells
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DOI：
10.1007/s00726-008-0158-y
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发表时间：
2009-04-01
期刊：
影响因子：
3.5
通讯作者：
Beninati, S.
中科院分区：
文献类型：
--
作者：
Forni, C.;Braglia, R.;Beninati, S.
黄酮类化合物属于植物多酚类化合物，具有6000多个已知结构。这些植物化学物质由于具有显著的生物活性，如抗过敏、抗炎、抗氧化、抗突变和抗癌等，引起了科学家的兴趣。在这项工作中，我们比较了两种黄酮类化合物--槲皮素和天花粉蛋白对高转移的B16-F10黑色素瘤小鼠细胞的抗癌作用。我们评估了与细胞增殖和分化相关的不同参数，如细胞数量、毒性、细胞内多胺含量和转谷氨酰胺酶(TG，EC 2.3.2.13)活性。与对照组相比，槲皮素组对肿瘤细胞生长的抑制作用更强，48h后抑制率为32%，72h后抑制率为39%(P<；0.001)。与之平行的是，用槲皮素处理的细胞在多胺含量上也表现出类似的下降。与对照组相比，48h后TG活性增加了4倍，72h后增加了一倍(P<；0.001)。天花粉蛋白处理组未表现出明显的抗增殖作用和TG活性的增加。用蛋白质组学的方法研究了肿瘤细胞在Qercetin处理后蛋白质表达谱的变化。共检测到60个蛋白质的表达变化，其中8个蛋白质表达下调，35个蛋白质表达上调，11个蛋白质“从头合成”，6个蛋白质被抑制。一个80 kDa的斑点，经Western印迹分析确定为TG2型，强度增加了4倍，证实了Tg在诱导癌细胞分化中所起的关键作用。
Flavonoids belong to the class of plant polyphenolic compounds with over 6,000 individual structures known. These phytochemicals have attracted the interest of the scientists, because they possess a remarkable spectrum of biological activities, such as antiallergic, antiinflammatory, antioxidant, antimutagenic and anticarcinogenic. In this work, we compared the anticancer potential of two flavonoids, quercetin and pelargonidin, on highly metastatic B16-F10 melanoma murine cells. We have evaluated different parameters related to cell proliferation and differentiation, such as cell number, toxicity, intracellular content of polyamines and transglutaminase (TG, EC 2.3.2.13) activity. The higher inhibition of tumor cell growth, with respect to control, was obtained with quercetin cell treatment, i.e. 32% reduction after 48 h and 39% reduction after 72 h of incubation (P < 0.001). In parallel, quercetin-treated cells showed a similar decrease in polyamine content. TG activity was fourfold increased, with respect to control, after 48 h and twofold increased after 72 h (P < 0.001). Pelargonidin treatment did not show significant antiproliferative effects and any increase in TG activity. Proteomic approach was used to investigate changes in protein expression profiles in tumor cells following quercetin treatment. Changes in expression of 60 proteins were detected, i.e. 8 proteins were down-regulated, 35 up-regulated, 11 "de novo" synthetized proteins and 6 suppressed proteins were present in treated cells. A 80 kDa spot, identified as TG type 2 by Western blot analysis, presented a fourfold increase in intensity, confirming the key role played by TG in the induction of cancer cell differentiation.