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ROS and Lipid Droplet accumulation induced by high glucose exposure in healthy colon and Colorectal Cancer Stem Cells

机译:通过高葡萄糖暴露在健康结肠和结肠直肠癌干细胞中引起的ROS和脂质液滴积累

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Lipid Droplets (LDs) are emerging as crucial players in colon cancer development and maintenance. Their expression has been associated with high tumorigenicity in Cancer Stem Cells (CSCs), so that they have been proposed as a new functional marker in Colorectal Cancer Stem Cells (CR-CSCs). They are also indirectly involved in the modulation of the tumor microenvironment through the production of pro-inflammatory molecules. There is growing evidence that a possible connection between metabolic alterations and malignant transformation exists, although the effects of nutrients, primarily glucose, on the CSC behavior are still mostly unexplored. Glucose is an essential fuel for cancer cells, and the connections with LDs in the healthy and CSC populations merit to be more deeply investigated. Here, we showed that a high glucose concentration activated the PI3K/AKT pathway and increased the expression of CD133 and CD44v6 CSC markers. Additionally, glucose was responsible for the increased amount of Reactive Oxygen Species (ROS) and LDs in both healthy and CR-CSC samples. We also investigated the gene modulations following the HG treatment and found out that the healthy cell gene profile was the most affected. Lastly, Atorvastatin, a lipid-lowering drug, induced the highest mortality on CR-CSCs without affecting the healthy counterpart.
机译:Lipid Droplet(LDS)作为结肠癌发育和维护的关键球员。它们的表达与癌症干细胞(CSC)中的高肿瘤性有关,因此已经提出了它们在结肠直肠癌干细胞(CR-CSCs)中的新功能标志物。它们也间接地通过产生促炎症分子来涉及调节肿瘤微环境。越来越多的证据表明,存在代谢改变和恶性转化之间的可能联系,尽管营养素主要是葡萄糖的影响,但在CSC行为上仍然是大多数未探索的。葡萄糖是癌细胞的必需燃料,与健康和CSC种群的LDS的关系是更深入的研究。这里,我们表明高葡萄糖浓度活化了PI3K / AKT途径,并增加了CD133和CD44V6 CSC标记的表达。另外,葡萄糖对健康和Cr-CSC样品中的反应性氧物质(ROS)和LDS的增加,负责。我们还研究了HG治疗后的基因调制,发现健康细胞基因型材受到最受影响的影响。最后,脂质降低药物的阿托伐他汀(Atorvastatin)诱导Cr-CSCs的最高死亡率而不影响健康的对应物。

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