Arcone Rosaria, Palma Margherita, Pagliara Valentina, Graziani Giulia, Masullo Mariorosario, Nardone Gerardo
Dipartimento di Scienze Motorie e del Benessere, Università di Napoli "Parthenope", Via Medina 40, 80133 Napoli, Italy.
CEINGE, Biotecnologie Avanzate, S.C. a R.L., Via G. Salvatore 486, 80145 Napoli, Italy.
Biochim Open. 2016 Nov 5;3:56-63. doi: 10.1016/j.biopen.2016.10.002. eCollection 2016 Dec.
Several studies demonstrated a correlation between green tea consumption and a reduced cancer risk. Among different components, green tea polyphenols have been identified as molecules responsible for the beneficial effects showed by the green tea against oxidative stress and cell invasiveness. In this study, we investigated the effects of green tea polyphenol extracts (GTPs) in human gastric MKN-28 cell line. To this aim, we have first evaluated the effect of GTPs on oxidative stress induced cell injury. The pre-treatment with 10 M catechin equivalents of GTPs exerts a protective effect on xanthine-xanthine oxidase induced cell cytotoxicity, thus confirming the anti-oxidant properties of GTPs. The effect of GTPs was also extended to the invasive ability of MKN-28 cells stimulated with TNF-α or LPS, as pro-inflammatory factors. Migration and matrigel invasion assays demonstrated that GTPs exposure (10 M) prevents the increase in cell invasiveness induced by TNF-α or LPS. Finally, we have analyzed the effect of GTPs on the levels of Matrix Metalloproteinases (MMP)-9/2, whose expression is up-regulated by TNF-α or LPS. Our results indicated that the pre-treatment with GTPs was able to reduce MMP-9/2 expression at both protein and enzyme activity levels in the conditioned media of TNF-α or LPS stimulated MKN-28 cells. In conclusion, our results demonstrated that green tea polyphenol extract reduces the invasiveness of gastric MKN-28 cancer cells through the reduction of TNF-α or LPS induced MMP-9/2 up-regulation. Therefore, these data support the hypothesis that GTPs could exert a protective role against the metastatic process in gastric cancer.
多项研究表明，饮用绿茶与降低癌症风险之间存在关联。在绿茶的不同成分中，绿茶多酚已被确认为是绿茶对氧化应激和细胞侵袭性所显示的有益作用的分子。在本研究中，我们调查了绿茶多酚提取物（GTPs）对人胃MKN - 28细胞系的影响。为此，我们首先评估了GTPs对氧化应激诱导的细胞损伤的影响。用10 μM儿茶素当量的GTPs进行预处理，对黄嘌呤 - 黄嘌呤氧化酶诱导的细胞毒性具有保护作用，从而证实了GTPs的抗氧化特性。GTPs的作用还扩展到了由肿瘤坏死因子-α（TNF-α）或脂多糖（LPS）作为促炎因子刺激的MKN - 28细胞的侵袭能力。迁移和基质胶侵袭试验表明，暴露于GTPs（10 μM）可防止TNF-α或LPS诱导的细胞侵袭性增加。最后，我们分析了GTPs对基质金属蛋白酶（MMP）-9/2水平的影响，其表达由TNF-α或LPS上调。我们的结果表明，用GTPs预处理能够在TNF-α或LPS刺激的MKN - 28细胞的条件培养基中，在蛋白质和酶活性水平上降低MMP - 9/2的表达。总之，我们的结果表明，绿茶多酚提取物通过降低TNF-α或LPS诱导的MMP - 9/2上调，降低了胃MKN - 28癌细胞的侵袭性。因此，这些数据支持了GTPs可能对胃癌转移过程发挥保护作用的假设。
