Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India.
School of Pharmacy and Technology Management, Narsee Moonjee Institute of Management Studies, Shirpur, India.
Front Biosci (Landmark Ed). 2019 Mar 1;24(6):1097-1157. doi: 10.2741/4771.
Diet and environment are two critical regulators that influence an individual's epigenetic profile. Besides the anterograde signaling, mitochondria act as a key regulator of epigenetic alterations in cancer either by controlling the concentration of the cofactors, activity of vital enzymes or by affecting the transcription of NF-kappaB and associated signaling molecules. As epigenetic modifications are the major drivers of aberrant gene expression, designing novel nutri-epigenomic strategies to modulate reversible epigenetic modifications will be important for effective cancer protection. In this regard, nutraceuticals such as flavonoids holds significant promise to modulate the epigenome through a network of interconnected anti-redox mechanisms. However, low solubility, rapid metabolism and poor absorption of flavonoids in gastrointestinal tract hinder their use in clinical settings. Therefore, it is imperative to develop nano-engineered systems which could considerably improve the targeted delivery of these bioactive compounds with better efficacy and pharmacokinetic properties. Concerted efforts in nano-engineering of flavonoids using polymer, lipid and complexation based approaches could provide successful bench-to-bedside translation of flavonoids as broad spectrum anti-cancer agents.
饮食和环境是影响个体表观遗传谱的两个关键调节因素。除了顺行信号外,线粒体还通过控制辅助因子的浓度、关键酶的活性或影响 NF-κB 的转录和相关信号分子来调节癌症中的表观遗传改变,从而成为表观遗传改变的关键调节剂。由于表观遗传修饰是异常基因表达的主要驱动因素,因此设计新型营养-表观基因组策略来调节可逆的表观遗传修饰对于有效的癌症保护将非常重要。在这方面,类黄酮等营养素有很大的希望通过相互关联的抗氧化还原机制网络来调节表观基因组。然而,类黄酮在胃肠道中的低溶解度、快速代谢和吸收不良阻碍了它们在临床环境中的应用。因此,开发纳米工程系统以改善这些生物活性化合物的靶向递送、提高疗效和药代动力学特性是至关重要的。使用聚合物、脂质和络合方法对类黄酮进行纳米工程的协同努力,可能为将类黄酮作为广谱抗癌药物进行成功的从实验室到病床的转化提供了机会。