Beneficial Regulation of Metabolic Profiles by Black Raspberries in Human Colorectal Cancer Patients.
Beneficial Regulation of Metabolic Profiles by Black Raspberries in Human Colorectal Cancer Patients.
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DOI：
10.1158/1940-6207.capr-15-0065
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Wang LS
中科院分区：
文献类型：
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作者：
Pan P;Skaer CW;Stirdivant SM;Young MR;Stoner GD;Lechner JF;Huang YW;Wang LS
在一组人类结直肠癌患者中，冻干黑树莓（BRB）的饮食干预已显示出有益的效果，包括促凋亡，抗增殖和抗血管生成。本研究的目的是研究同一队列患者中BRB介导的代谢物变化。28例结直肠癌患者口服BRB散60 g/d，疗程1-9周。在BRB干预前后采集尿液和血浆标本。对每份标本进行了基于质谱的非靶向代谢组学分析。每份标本中共注释了400多种代谢物。其中34种和6种代谢产物分别在尿液和血浆中被BRB显著改变。BRB后尿液和BRB后血浆中4-甲基儿茶酚硫酸盐水平的增加与BRB后肿瘤中较高水平的凋亡标记物（TUNEL）显著相关。一种三羧酸（TCA）循环代谢产物顺乌头酸在BRB后尿液中增加。此外，BRB衍生的多酚被吸收和代谢为各种苯甲酸盐物种，这是显着增加后BRB标本。苯甲酸盐水平的增加与氨基酸代谢物水平的增加呈正相关。这些结果表明，BRBs诱导显着的代谢变化，影响能量产生途径。这项研究支持了BRB可能通过调节多种代谢物对结直肠癌患者有益的假设。
Dietary intervention of freeze-dried black raspberries (BRBs) in a group of human colorectal cancer patients has demonstrated beneficial effects, including pro-apoptosis, anti-proliferation and anti-angiogenesis. The aim of this study was to investigate BRB-mediated metabolite changes from this same cohort of patients. 28 colorectal cancer patients were given 60 g BRB powder daily for 1–9 weeks. Urine and plasma specimens were collected before and after BRB intervention. A mass spectrometry-based nontargeted metabolomic analysis was conducted on each specimen. A total of more than 400 metabolites were annotated in each specimen. Of these 34 and 6 metabolites were significantly changed by BRBs in urine and plasma, respectively. Increased levels of 4-methylcatechol sulfate in both post-BRB urine and post-BRB plasma were significantly correlated with a higher level of apoptotic marker (TUNEL) in post-BRB tumors. One tricarboxylic acid (TCA) cycle metabolites, Cis-aconitate, was increased in post-BRB urine. Furthermore, BRB-derived polyphenols were absorbed and metabolized to various benzoate species, which were significantly increased in post-BRB specimens. Increased benzoate levels were positively correlated with enhanced levels of amino acid metabolites. These results suggest that BRBs induce significant metabolic changes and affect energy generating pathways. This study supports the hypothesis that BRBs might be beneficial to colorectal cancer patients through the regulation of multiple metabolites.