4-Vinylguaiacol, an Active Metabolite of Ferulic Acid by Enteric Microbiota and Probiotics, Possesses Significant Activities against Drug-Resistant Human Colorectal Cancer Cells.
4-Vinylguaiacol, an Active Metabolite of Ferulic Acid by Enteric Microbiota and Probiotics, Possesses Significant Activities against Drug-Resistant Human Colorectal Cancer Cells.
复制标题
4-乙烯基愈创木酚是肠道微生物群和益生菌对阿魏酸的活性代谢物，对耐药人类结直肠癌细胞具有显着活性
DOI：
10.1021/acsomega.0c04394
复制
发表时间：
2021-02-23
期刊：
影响因子：
4.1
通讯作者：
Yuan CS
中科院分区：
文献类型：
--
作者：
Luo Y;Wang CZ;Sawadogo R;Yuan J;Zeng J;Xu M;Tan T;Yuan CS
阿魏酸是一种羟基肉桂酸，在蔬菜、谷物和药用植物中含量丰富。新出现的证据表明，阿魏酸可能对结直肠癌产生有益的影响。然而，阿魏酸的抗癌活性相对较低，其口服后的代谢在很大程度上是未知的。本研究模拟肠道环境，利用人体肠道微生物菌群和商业益生菌将阿魏酸代谢为其代谢产物，并评价其抗癌活性。阿魏酸可生物转化为4-乙烯基愈创木酚（2-甲氧基-4-乙烯基苯酚），采用高效液相色谱法（HPLC）测定生物转化提取物中阿魏酸和4-乙烯基愈创木酚的含量。以化疗敏感细胞株HCT-116和化疗耐药细胞株HT-29为材料，采用改良三色染色法检测细胞增殖情况。流式细胞仪检测细胞周期和凋亡诱导率。HPLC数据显示，阿魏酸转化为4-乙烯基愈创木酚，肠道菌群和4种益生菌的转化率为1.3%-36.8%。阿魏酸和4-乙烯基愈创木酚对这两种细胞系都具有剂量和时间相关的抗癌活性，而4-乙烯基愈创木酚显示出比阿魏酸更有效的作用。有趣的是，4-乙烯基愈创木酚对HT-29细胞系的抗增殖作用显著高于对HCT-116的抗增殖作用。代谢产物4-乙烯基愈创木酚对HT-29细胞的IC 50为350 μM，是其母体化合物的3.7倍。4-乙烯基愈创木酚抑制癌细胞生长的潜力是通过将细胞周期阻滞在G1期和诱导凋亡来介导的。这项研究的数据表明，口服阿魏酸提供了一种很有前途的方法，通过肠道微生物转化为4-乙烯基愈创木酚来增加其抗癌活性，并且生物转化也可以通过选定的商业益生菌来实现。4-乙烯基愈创木酚是来自阿魏酸的一种潜在抗癌代谢产物，用于化疗耐药结肠癌细胞。
Ferulic acid, a hydroxycinnamic acid, is abundant in vegetables, grains, and medicinal plants. Emerging evidence suggests that ferulic acid may exert beneficial effects against colorectal cancer. However, the anticancer activity of ferulic acid is relatively low, and its metabolism after oral administration is largely unknown. In this study, mimicking the enteric environment, human intestinal microflora and commercial probiotics were used to metabolize ferulic acid to its metabolites, and their anticancer activities were evaluated. Ferulic acid can be biotransformed to 4-vinylguaiacol (2-methoxy-4-vinylphenol), and the contents of ferulic acid and 4-vinylguaiacol in bio-transformed extracts were determined by high-performance liquid chromatography (HPLC). Using the chemotherapy-sensitive cell line HCT-116 and the chemo-resistant cell line HT-29, the cell proliferation was determined by the modified trichrome stain assay. The cell cycle and induction of apoptosis were assayed using flow cytometry. HPLC data showed that there was a marked transformation from ferulic acid to 4-vinylguaiacol, and the conversion rates of intestinal microflora and four probiotics were from 1.3 to 36.8%. Both ferulic acid and 4-vinylguaiacol possessed dose- and time-related anticancer activities on the two cell lines, while 4-vinylguaiacol showed more potent effects than ferulic acid. Interestingly, 4-vinylguaiacol exhibited significantly higher antiproliferative effects on the HT-29 cell line than that on HCT-116. The IC50 of the metabolite 4-vinylguaiacol on HT-29 cells was 350 μM, 3.7-fold higher than its parent compound. The potential of cancer cell growth inhibition of 4-vinylguaiacol was mediated by cell cycle arrest at the G1 phase and induction of apoptosis. Data from this study indicate that the oral administration of ferulic acid offers a promising approach to increase its anticancer activity through gut microbial conversion to 4-vinylguaiacol, and the biotransformation could also be achieved by selected commercial probiotics. 4-Vinylguaiacol is a potential anticancer metabolite from ferulic acid for chemotherapy-resistant colon cancer cells.
登录
查看更多内容
影响因子：
3.7
作者：
Sniffen, Jason C.;McFarland, Lynne V.;Goldstein, Ellie J. C.
通讯作者：
Goldstein, Ellie J. C.
影响因子：
5.9
作者：
Plaza-Díaz J;Ruiz-Ojeda FJ;Gil-Campos M;Gil A
通讯作者：
Gil A
影响因子：
5.6
作者：
Alimbetov D;Askarova S;Umbayev B;Davis T;Kipling D
通讯作者：
Kipling D
影响因子：
--
作者：
Eroglu, Canan;Secme, Mucahit;Dodurga, Yavuz
通讯作者：
Dodurga, Yavuz
影响因子：
2.7
作者：
Sudhagar, S.;Sathya, S.;Lakshmi, B. S.
通讯作者：
Lakshmi, B. S.