Phenomenome Discoveries, Inc, Saskatoon, Saskatchewan, Canada.
J Exp Clin Cancer Res. 2011 May 17;30(1):59. doi: 10.1186/1756-9966-30-59.
Circulating levels of novel long-chain hydroxy fatty acids (called GTAs) were recently discovered in the serum of healthy subjects which were shown to be reduced in subjects with colorectal cancer (CRC), independent of tumor burden or disease stage. The levels of GTAs were subsequently observed to exhibit an inverse association with age in the general population. The current work investigates the biological activity of these fatty acids by evaluating the effects of enriched human serum extracts on cell growth and inflammation.
GTAs were extracted from commercially available bulk human serum and then chromatographically separated into enriched (GTA-positive) and depleted (GTA-negative) fractions. SW620, MCF7 and LPS stimulated RAW264.7 cells were treated with various concentrations of the GTA-positive and GTA-negative extracts, and the effects on cell growth and inflammation determined.
Enriched fractions resulted in poly-ADP ribose polymerase (PARP) cleavage, suppression of NFκB, induction of IκBα, and reduction in NOS2 mRNA transcript levels. In RAW264.7 mouse macrophage cells, incubation with enriched fractions prior to treatment with LPS blocked the induction of several pro-inflammatory markers including nitric oxide, TNFα, IL-1β, NOS2 and COX2.
Our results show that human serum extracts enriched with endogenous long-chain hydroxy fatty acids possess anti-inflammatory and anti-proliferative activity. These findings support a hypothesis that the reduction of these metabolites with age may result in a compromised ability to defend against uncontrolled cell growth and inflammation, and could therefore represent a significant risk for the development of CRC.
新型长链羟基脂肪酸（称为 GTAs）的循环水平最近在健康受试者的血清中被发现，并且独立于肿瘤负担或疾病阶段，在结直肠癌（CRC）患者中发现其水平降低。随后观察到这些脂肪酸的水平在普通人群中与年龄呈负相关。目前的工作通过评估富含人血清提取物对细胞生长和炎症的影响来研究这些脂肪酸的生物学活性。
从市售的大量人血清中提取 GTAs，然后通过色谱法将其分离为富含（GTA 阳性）和耗尽（GTA 阴性）部分。用各种浓度的 GTA 阳性和 GTA 阴性提取物处理 SW620、MCF7 和 LPS 刺激的 RAW264.7 细胞，并测定对细胞生长和炎症的影响。
富含 GTA 的部分导致多聚 ADP 核糖聚合酶（PARP）切割、NFκB 抑制、IκBα诱导和 NOS2 mRNA 转录水平降低。在 RAW264.7 小鼠巨噬细胞中，在用 LPS 处理之前用富含 GTA 的部分孵育可阻断几种促炎标志物的诱导，包括一氧化氮、TNFα、IL-1β、NOS2 和 COX2。
我们的结果表明，富含内源性长链羟基脂肪酸的人血清提取物具有抗炎和抗增殖活性。这些发现支持了这样一种假设，即这些代谢物随年龄的减少可能导致对抗不受控制的细胞生长和炎症的能力受损，因此可能代表 CRC 发展的重大风险。
