Laboratory of Vascular Biology and Angiogenesis, IRCCS MultiMedica, Milan, Italy.
Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
Cancer Lett. 2018 Aug 10;429:100-116. doi: 10.1016/j.canlet.2018.04.018. Epub 2018 Apr 18.
Carnitines play an important role in the energy exchange in cells, and are involved in the transport of fatty acids across the inner mitochondrial membrane. l-Acetylcarnitine (ALCAR) is an acetic acid ester of carnitine that has higher bioavailability and is considered a fat-burning energizer supplement. We previously found that in serum samples from prostate cancer (PCa) patients, 3 carnitine family members were significantly decreased, suggesting a potential protective role of carnitine against PCa. Several studies support beneficial effects of carnitines on cancer, no study has investigated the activities of carnitine on tumor angiogenesis. We examined whether ALCAR acts as an "angiopreventive" compound and studied the molecular mechanisms involved. We found that ALCAR was able to limit inflammatory angiogenesis by reducing stimulated endothelial cell and macrophage infiltration in vitro and in vivo. Molecularly, we show that ALCAR downregulates VEGF, VEGFR2, CXCL12, CXCR4 and FAK pathways. ALCAR blocked the activation of NF-κB and ICAM-1 and reduced the adhesion of a monocyte cell line to endothelial cells. This is the first study showing that ALCAR has anti-angiogenic and anti-inflammatory properties and might be an attractive candidate for cancer angioprevention.
肉碱在细胞能量交换中发挥重要作用，并参与脂肪酸穿过线粒体内膜的转运。乙酰左旋肉碱（ALCAR）是肉碱的乙酸酯，具有更高的生物利用度，被认为是一种燃脂能量补充剂。我们之前发现，在前列腺癌（PCa）患者的血清样本中，有 3 种肉碱家族成员显著减少，这表明肉碱对 PCa 可能具有潜在的保护作用。几项研究支持肉碱对癌症的有益作用，但没有研究调查肉碱对肿瘤血管生成的作用。我们研究了 ALCAR 是否作为一种“血管预防”化合物发挥作用，并研究了涉及的分子机制。我们发现，ALCAR 能够通过减少体外和体内刺激的内皮细胞和巨噬细胞浸润来限制炎症性血管生成。从分子水平上，我们表明 ALCAR 下调 VEGF、VEGFR2、CXCL12、CXCR4 和 FAK 途径。ALCAR 阻断 NF-κB 和 ICAM-1 的激活，并减少单核细胞系与内皮细胞的黏附。这是第一项表明 ALCAR 具有抗血管生成和抗炎特性的研究，可能是癌症血管预防的有吸引力的候选药物。
