Javed Zeeshan, Khan Khushbukhat, Herrera-Bravo Jesús, Naeem Sajid, Iqbal Muhammad Javed, Sadia Haleema, Qadri Qamar Raza, Raza Shahid, Irshad Asma, Akbar Ali, Reiner Željko, Al-Harrasi Ahmed, Al-Rawahi Ahmed, Satmbekova Dinara, Butnariu Monica, Bagiu Iulia Cristina, Bagiu Radu Vasile, Sharifi-Rad Javad
Office of Research Innovation and Commercialization (ORIC), Lahore Garrison University, Sector-C, DHA Phase-VI, Lahore, Pakistan.
Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, 44000, Pakistan.
Cancer Cell Int. 2021 Jul 21;21(1):388. doi: 10.1186/s12935-021-02091-8.
Cancers are complex diseases orchestrated by a plethora of extrinsic and intrinsic factors. Research spanning over several decades has provided better understanding of complex molecular interactions responsible for the multifaceted nature of cancer. Recent advances in the field of next generation sequencing and functional genomics have brought us closer towards unravelling the complexities of tumor microenvironment (tumor heterogeneity) and deregulated signaling cascades responsible for proliferation and survival of tumor cells. Phytochemicals have begun to emerge as potent beneficial substances aimed to target deregulated signaling pathways. Isoflavonoid genistein is an essential phytochemical involved in regulation of key biological processes including those in different types of cancer. Emerging preclinical evidence have shown its anti-cancer, anti-inflammatory and anti-oxidant properties. Testing of this substance is in various phases of clinical trials. Comprehensive preclinical and clinical trials data is providing insight on genistein as a modulator of various signaling pathways both at transcription and translation levels. In this review we have explained the mechanistic regulation of several key cellular pathways by genistein. We have also addressed in detail various microRNAs regulated by genistein in different types of cancer. Moreover, application of nano-formulations to increase the efficiency of genistein is also discussed. Understanding the pleiotropic potential of genistein to regulate key cellular pathways and development of efficient drug delivery system will bring us a step towards designing better chemotherapeutics.
癌症是由大量外在和内在因素共同作用导致的复杂疾病。数十年来的研究使我们对造成癌症多面性的复杂分子相互作用有了更深入的了解。新一代测序和功能基因组学领域的最新进展让我们在揭示肿瘤微环境的复杂性(肿瘤异质性)以及导致肿瘤细胞增殖和存活的信号级联失调方面又迈进了一步。植物化学物质已开始作为针对失调信号通路的有效有益物质崭露头角。异黄酮染料木黄酮是一种重要的植物化学物质,参与调控包括不同类型癌症相关过程在内的关键生物学过程。新出现的临床前证据表明了其抗癌、抗炎和抗氧化特性。该物质的测试正处于临床试验的各个阶段。全面的临床前和临床试验数据为染料木黄酮作为转录和翻译水平上各种信号通路的调节剂提供了深入见解。在这篇综述中,我们阐述了染料木黄酮对几种关键细胞通路的机制调控。我们还详细讨论了染料木黄酮在不同类型癌症中调控的各种微小RNA。此外,还讨论了应用纳米制剂提高染料木黄酮的效率。了解染料木黄酮调控关键细胞通路的多效潜能以及开发高效的药物递送系统将使我们朝着设计更好的化疗药物迈进一步。