A comparison of the anticancer properties of isoxanthohumol and 8-prenylnaringenin using in vitro models of colon cancer
A comparison of the anticancer properties of isoxanthohumol and 8-prenylnaringenin using in vitro models of colon cancer
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DOI：
10.1002/biof.1084
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发表时间：
2013-07-01
期刊：
影响因子：
6
通讯作者：
Rowland, Ian
中科院分区：
文献类型：
--
作者：
Allsopp, Philip;Possemiers, Sam;Rowland, Ian
啤酒花(Humulus lupulus L.)是啤酒中的一种基本成分，含有许多具有潜在生物活性的异戊烯基黄酮类化合物，主要是弱雌激素的异黄腐酚(IX)，它可以被结肠微生物区系转化为更强的雌激素样的8-PN。本研究的目的是利用代表结直肠癌发生的关键阶段的体外模型，即细胞生长和活力(四甲基偶氮唑盐比色法)、细胞周期进展(DNA含量测定)、DNA损伤(彗星试验)和侵袭(Matrigel试验)来研究8-PN和IX的生物学活性。在较高剂量(分别为40和50M)的8-PN和IX处理后，Caco-2细胞存活率显著降低，尽管这两种化合物对细胞周期的影响不同。IX处理后细胞存活率下降与浓度依赖的G2/M期增加和亚G1期细胞比例增加有关，而8-PN处理与G0/G1期和亚G1期细胞比例增加相关。在所测试的所有8-PN浓度(5-40M)下，均观察到显著的抗遗传毒性活性。尽管在25M时，IX处理也有显著的抗遗传毒性作用，但在更高的剂量下，IX本身也表现出遗传毒性活性。两种化合物均以剂量依赖的方式抑制HT115细胞的侵袭，与未经处理的细胞相比，IX和8-PN的侵袭力分别降低了52%和46%。本研究证明IX及其肠道微生物代谢产物8-PN对结肠癌发生的关键阶段模型均有一定的抗癌作用。(C)2013年生物因素，39(4)：441-447,2013年
The hops plant (Humulus lupulus L.) is an essential ingredient in beer and contains a number of potentially bioactive prenylflavonoids, the predominant being the weakly estrogenic isoxanthohumol (Ix), which can be converted to the more strongly estrogenic 8-PN by the colonic microbiota. The aim of this study was to investigate the biological activity of 8-PN and Ix using in vitro models representing key stages of colorectal carcinogenesis, namely cell growth and viability (MTT assay), cell-cycle progression (DNA content assay), DNA damage (Comet assay), and invasion (Matrigel assay). A significant decrease in Caco-2 cell viability was noted after both 8-PN and Ix treatments at the higher doses (40 and 50 M, respectively) although the impact on cell cycle differed between the two compounds. The decreased cell viability observed after Ix treatment was associated with a concentration-dependent increase in G2/M and an increased sub-G1 cell-cycle fraction, whereas treatment with 8-PN was associated with an elevated G0/G1 and an increased sub-G1 cell-cycle fraction. Significant antigenotoxic activity was noted at all 8-PN concentrations tested (5-40 M). Although significant antigenotoxic activity was also noted with Ix treatment at 25 M, at a higher dose, Ix itself exerted genotoxic activity. In a dose-dependent manner, both compounds inhibited HT115 cell invasion with reductions up to 52 and 46% for Ix and 8-PN, respectively, in comparison to untreated cells. This study demonstrated that both Ix and its gut microbial metabolite 8-PN exert anticancer effects on models of key stages of colon tumourigenesis. (c) 2013 BioFactors, 39(4):441-447, 2013