Enhancing the Cancer Cell Growth Inhibitory Effects of Table Grape Anthocyanins
Enhancing the Cancer Cell Growth Inhibitory Effects of Table Grape Anthocyanins
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DOI：
10.1111/1750-3841.14294
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发表时间：
2018-09-01
影响因子：
3.9
通讯作者：
Forester, Sarah C.
中科院分区：
文献类型：
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作者：
Grimes, Karnell L.;Stuart, Connor M.;Forester, Sarah C.
患乳腺癌和结肠癌的风险可以通过大量摄入水果和蔬菜来降低。葡萄等水果含有丰富的生物活性化合物，如花青素。花青素的潜在抗癌活性可能受到其在肠道和肝脏代谢的限制。一种代谢转化是由于酶儿茶酚- o -甲基转移酶（COMT），它甲基化多酚，如花青素。恩他卡酮是临床上使用的COMT抑制剂，并已被证明可以调节食物来源的多酚的甲基化。在本研究中，我们比较了恩他卡彭对花青素处理过的结肠癌（Caco-2和HT-29）和乳腺癌（MDA-MB-231）癌细胞活力的影响。细胞用花青素-3-葡萄糖苷、飞鸽苷-3-葡萄糖苷或富含花青素的葡萄提取物处理，在没有或存在恩他卡彭的情况下。采用噻唑蓝溴化四唑（MTT）法测定细胞活力。恩他卡酮与花青素联用对Caco-2细胞的生长抑制作用大于相加作用。在MDA-MB-231细胞系中，恩他卡酮同样增强了花青素提取物的生长抑制活性。恩他卡朋单独使用时也有抗增殖作用。测定细胞培养基中总氢过氧化物含量。浓度越高的处理导致总氢过氧化物水平越高，表明氧化应激可能是生长抑制的重要机制。综上所述，果源花青素在临床上应用的药物恩他卡酮可提高其对人癌细胞的抗增殖活性。恩他卡酮/花青素联合用药的体内疗效和机制有待进一步研究。葡萄的化学成分对我们的健康有益，并已被证明可以降低患某些癌症的风险。它们对健康的有益影响也可以通过摄入其他分子来增强其生物利用度。
The risk for breast and colon cancer may be lowered in part by high intake of fruits and vegetables. Fruits such as grapes are abundant in bioactive compounds such as anthocyanins. The potential anticancer activity of anthocyanins may be limited by their metabolism in the gut and liver. One metabolic transformation is due to the enzyme catechol-O-methyltransferase (COMT), which methylates polyphenols such as anthocyanins. Entacapone is a clinically used inhibitor of COMT, and has been shown to modulate the methylation of food-derived polyphenols. In this study, we compared the effect of entacapone on the cell viability of colon (Caco-2 and HT-29) and breast (MDA-MB-231) cancer cell lines treated with anthocyanins. Cells were treated with either cyanidin-3-glucoside, delphinidin-3-glucoside, or an anthocyanin-rich grape extract, in the absence or presence of entacapone. Cell viability was assessed using the thiazolyl blue tetrazolium bromide (MTT) assay. Entacapone in combination with the anthocyanins had a greater than additive effect on growth inhibition of the Caco-2 cells. In the MDA-MB-231 cell line, entacapone similarly enhanced the growth inhibitory activity of the anthocyanin extract. Entacapone also had antiproliferative effects when used as a single treatment. Total hydroperoxides was quantified in the cell culture media. Greater concentrations of the treatments resulted in higher levels of total hydroperoxides, indicating that oxidative stress may be an important mechanism for growth inhibition. In conclusion, the antiproliferative activity of fruit-derived anthocyanins was improved in human cancer cell lines by the clinically used drug entacapone. The efficacy and mechanisms of entacapone/anthocyanin combinations should be carefully studied in vivo.Practical ApplicationChemical components of grapes are good for our health and have been shown to lower risk for certain cancers. Their beneficial health effects could also be enhanced by consuming other molecules that improve their bioavailability.