Maurya Akhilendra Kumar, Vinayak Manjula
a Laboratory of Biochemistry and Molecular Biology , Centre for Advanced Study in Zoology, Institute of Science, Banaras Hindu University , Varanasi , India.
Nutr Cancer. 2017 Apr;69(3):470-480. doi: 10.1080/01635581.2017.1267775. Epub 2017 Jan 20.
AKT signaling is important to maintaining normal physiology. Hyperactivation of AKT signaling is frequent in cancer, which maintains a high oxidative state in a tumor microenvironment that is needed for tumor adaptation. Therefore, antioxidants are proposed to exhibit anticancer properties by interfering with the tumor microenvironment. Quercetin is an ubiquitous bioactive antioxidant rich in vegetables and beverages. The present study aimed to analyze cancer preventive property of quercetin in ascite cells of Dalton's lymphoma-bearing mice. Protein level was determined by Western blotting. Nitric oxide (NO) level was estimated spectrophotometrically using Griess reagent. Results show downregulation in phosphorylation of AKT and PDK1 by quercetin, which was consistent with decreased phosphorylation of downstream survival factors such as BAD, GSK-3β, mTOR, and IkBα. Further, quercetin attenuated the levels of angiogenic factor VEGF-A and inflammatory enzymes COX-2 and iNOS as well as NO levels, whereas it increased the levels of phosphatase PTEN. Overall results suggest that quercetin modulates AKT signaling leading to attenuation of cell survival, inflammation, and angiogenesis in lymphoma-bearing mice.
AKT信号传导对于维持正常生理功能至关重要。AKT信号传导的过度激活在癌症中很常见，它在肿瘤微环境中维持一种高氧化状态，而这是肿瘤适应所必需的。因此，有人提出抗氧化剂可通过干扰肿瘤微环境来展现抗癌特性。槲皮素是一种广泛存在于蔬菜和饮品中的生物活性抗氧化剂。本研究旨在分析槲皮素对荷道尔顿淋巴瘤小鼠腹水细胞的防癌特性。通过蛋白质印迹法测定蛋白质水平。使用格里斯试剂通过分光光度法估算一氧化氮（NO）水平。结果显示，槲皮素可下调AKT和PDK1的磷酸化水平，这与下游存活因子如BAD、GSK - 3β、mTOR和IkBα磷酸化水平降低相一致。此外，槲皮素可降低血管生成因子VEGF - A、炎性酶COX - 2和iNOS的水平以及NO水平，而增加磷酸酶PTEN的水平。总体结果表明，槲皮素可调节AKT信号传导，从而减轻荷淋巴瘤小鼠的细胞存活、炎症和血管生成。
