Quercetin Interrupts the Positive Feedback Loop Between STAT3 and IL-6, Promotes Autophagy, and Reduces ROS, Preventing EBV-Driven B Cell Immortalization
Quercetin Interrupts the Positive Feedback Loop Between STAT3 and IL-6, Promotes Autophagy, and Reduces ROS, Preventing EBV-Driven B Cell Immortalization
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DOI：
10.3390/biom9090482
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发表时间：
2019-09-01
期刊：
影响因子：
5.5
通讯作者：
Cirone, Mara
中科院分区：
文献类型：
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作者：
Granato, Marisa;Gilardini Montani, Maria Saveria;Cirone, Mara
致癌性伽玛疱疹病毒 Epstein-Barr 病毒 (EBV) 在体外将 B 淋巴细胞永生化为类淋巴母细胞系 (LCL)，这一模型为探索驱动病毒肿瘤发生的分子机制提供了机会。在这项研究中，我们探讨了槲皮素（一种广泛分布的黄酮类化合物，具有抗氧化、抗炎和抗癌特性）在防止 EBV 驱动的 B 细胞永生化方面的潜力。获得的结果表明，槲皮素抑制 EBV 感染诱导的信号转导器和转录激活剂 3 (STAT3) 的激活，并减少已知对永生化过程至关重要的分子，例如白细胞介素 6 (IL-6) 和活性氧化物质 (ROS)。此外，我们发现槲皮素促进自噬并抵消sequestosome1/p62 (SQSTM1/p62)的积累，最终导致B细胞永生化的阻止。这些发现表明槲皮素可能有潜力用于对抗 EBV 驱动的淋巴瘤发生，特别是如果其稳定性得到改善的话。
The oncogenic gammaherpesvirus Epstein-Barr virus (EBV) immortalizes in vitro B lymphocytes into lymphoblastoid cell lines (LCLs), a model that gives the opportunity to explore the molecular mechanisms driving viral tumorigenesis. In this study, we addressed the potential of quercetin, a widely distributed flavonoid displaying antioxidant, anti-inflammatory, and anti-cancer properties, in preventing EBV-driven B cell immortalization. The results obtained indicated that quercetin inhibited thectivation of signal transducer and activator of transcription 3 (STAT3) induced by EBV infection and reduced molecules such as interleukin-6 (IL-6) and reactive oxidative species (ROS) known to be essential for the immortalization process. Moreover, we found that quercetin promoted autophagy and counteracted the accumulation of sequestosome1/p62 (SQSTM1/p62), ultimately leading to the prevention of B cell immortalization. These findings suggest that quercetin may have the potential to be used to counteract EBV-driven lymphomagenesis, especially if its stability is improved.