Baba Abdul Basit, Nivetha Ramesh, Chattopadhyay Indranil, Nagini Siddavaram
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India.
Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India.
Food Chem Toxicol. 2017 Nov;109(Pt 1):534-543. doi: 10.1016/j.fct.2017.09.054. Epub 2017 Sep 30.
Blueberries, a rich source of anthocyanins have attracted considerable attention as functional foods that confer immense health benefits including anticancer properties. Herein, we assessed the potential of blueberry and its major constituent malvidin to target STAT-3, a potentially druggable oncogenic transcription factor with high therapeutic index. We demonstrate that blueberry abrogates the JAK/STAT-3 pathway and modulates downstream targets that influence cell proliferation and apoptosis in a hamster model of oral oncogenesis. Further, we provide mechanistic evidence that blueberry and malvidin function as STAT-3 inhibitors in the oral cancer cell line SCC131. Blueberry and malvidin suppressed STAT-3 phosphorylation and nuclear translocation thereby inducing cell cycle arrest and mitochondrial-mediated apoptosis. However, the combination of blueberry and malvidin with the STAT-3 inhibitor S3I-201 was more efficacious in STAT-3 inhibition relative to single agents. The present study has provided leads for the development of novel combinations of compounds that can serve as inhibitors of STAT-mediated oncogenic signalling.
蓝莓富含花青素，作为具有巨大健康益处（包括抗癌特性）的功能性食品已引起广泛关注。在此，我们评估了蓝莓及其主要成分锦葵色素靶向信号转导和转录激活因子3（STAT-3）的潜力，STAT-3是一种具有高治疗指数、潜在可成药的致癌转录因子。我们证明，在口腔肿瘤发生的仓鼠模型中，蓝莓可消除JAK/STAT-3信号通路并调节影响细胞增殖和凋亡的下游靶点。此外，我们提供了机制证据，表明蓝莓和锦葵色素在口腔癌细胞系SCC131中作为STAT-3抑制剂发挥作用。蓝莓和锦葵色素抑制STAT-3磷酸化和核转位，从而诱导细胞周期停滞和线粒体介导的凋亡。然而，相对于单一药物，蓝莓和锦葵色素与STAT-3抑制剂S3I-201联合使用在抑制STAT-3方面更有效。本研究为开发可作为STAT介导的致癌信号抑制剂的新型化合物组合提供了线索。
