Shan Xiaoyun, Li Yuan, Meng Xulian, Wang Pengqi, Jiang Pan, Feng Qing
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China.
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China.
Food Chem Toxicol. 2014 Apr;66:194-202. doi: 10.1016/j.fct.2014.01.046. Epub 2014 Feb 4.
Acrylamide, a proven rodent carcinogen, is present in carbohydrate-rich food heated at high temperatures. It can be metabolized into glycidamide mainly by cytochrome P450 2E1 (CYP2E1). The fact that acrylamide is a potential carcinogen to human-beings draws public attention recently. This study aimed to elucidate the effect of acrylamide at low doses on proliferation of HepG2 cells, and to test whether the two well-studied chemopreventive agents, curcumin and (-)-epigallocatechin-3-gallate (EGCG), would have antagonistic effects against acrylamide. The results showed that lower concentration of acrylamide (⩽100μM) significantly increased the proliferation of HepG2 cells, but not of the other cancer cells (MDA-231, HeLa, A549, and PC-3). Only in HepG2 cells, low concentration of acrylamide was able to induce CYP2E1 expression significantly. Knockdown of CYP2E1 restrained acrylamide to increase viability of HepG2 cells. In addition, acrylamide raised expression of epidermal growth factor receptor (EGFR), cyclin D1 and nuclear factor-κB (NF-κB), which contributed to cell proliferation. Both curcumin and EGCG effectively reduced acrylamide-induced proliferation, as well as protein expression of CYP2E1, EGFR, cyclin D1 and NF-κB. All these results suggest that low concentration of acrylamide may contribute to progression of hepatocellular carcinoma (HCC). Curcumin or EGCG could prevent acrylamide triggering this effect.
丙烯酰胺是一种已被证实的啮齿动物致癌物，存在于高温加热的富含碳水化合物的食物中。它主要通过细胞色素P450 2E1（CYP2E1）代谢为环氧丙酰胺。丙烯酰胺对人类是一种潜在致癌物这一事实最近引起了公众的关注。本研究旨在阐明低剂量丙烯酰胺对HepG2细胞增殖的影响，并测试两种经过充分研究的化学预防剂姜黄素和（-）-表没食子儿茶素-3-没食子酸酯（EGCG）是否对丙烯酰胺具有拮抗作用。结果表明，较低浓度的丙烯酰胺（⩽100μM）显著增加了HepG2细胞的增殖，但对其他癌细胞（MDA-231、HeLa、A549和PC-3）没有影响。仅在HepG2细胞中，低浓度的丙烯酰胺能够显著诱导CYP2E1表达。敲低CYP2E1可抑制丙烯酰胺增加HepG2细胞的活力。此外，丙烯酰胺上调了表皮生长因子受体（EGFR）、细胞周期蛋白D1和核因子-κB（NF-κB）的表达，这有助于细胞增殖。姜黄素和EGCG均有效降低了丙烯酰胺诱导的增殖以及CYP2E1、EGFR、细胞周期蛋白D和NF-κB的蛋白表达。所有这些结果表明，低浓度的丙烯酰胺可能促进肝细胞癌（HCC）的进展。姜黄素或EGCG可以预防丙烯酰胺引发这种效应。
