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丁布对化学预防潜力的分子机制:当前趋势和未来展望。

Molecular mechanisms underlying chemopreventive potential of butein: Current trends and future perspectives.

机构信息

Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, Haryana, 133207, India.

Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai, 56, Maharashtra, India.

出版信息

Chem Biol Interact. 2021 Dec 1;350:109699. doi: 10.1016/j.cbi.2021.109699. Epub 2021 Oct 11.

Abstract

Despite extensive efforts, cancer is still often considered as an incurable disease and initiation of novel drug development programs is crucial to improve the prognosis and clinical outcome of patients. One of the major approaches in designing the novel cancer drugs has historically comprised studies of natural agents with diverse anticancer properties. As only a marginal part of natural compounds has been investigated, this approach still represents an attractive source of new potential antitumor molecules. In this review article, different anticancer effects of plant-derived chalcone, butein, are discussed, including its growth inhibitory action, proapoptotic, antiangiogenic and antimetastatic activities in a variety of cancer cells. The molecular mechanisms underlying these effects are presented in detail, revealing interactions of butein with multiple cellular targets (Bcl-2/Bax, caspases, STAT3, cyclins, NF-κB, COX-2, MMP-9, VEGF/R etc.) and regulation of a wide range of intracellular signal transduction pathways. These data altogether allow a good basis for initiating further in vivo studies as well as clinical trials. Along with the efforts to overcome low bioavailability issues generally characteristic to plant metabolites, butein can be considered as a potential lead compound for safe and more efficient cancer drugs in the future.

摘要

尽管已经做出了广泛的努力,但癌症仍然常常被认为是一种无法治愈的疾病,因此开展新的药物开发计划对于改善患者的预后和临床结果至关重要。在设计新型癌症药物时,主要方法之一是研究具有多种抗癌特性的天然药物。由于仅对天然化合物的一小部分进行了研究,因此这种方法仍然是寻找新的潜在抗肿瘤分子的有吸引力的来源。在这篇综述文章中,讨论了植物来源的查尔酮、布替丁的不同抗癌作用,包括其在多种癌细胞中的生长抑制作用、促凋亡作用、抗血管生成作用和抗转移作用。详细介绍了这些作用的分子机制,揭示了布替丁与多种细胞靶标(Bcl-2/Bax、胱天蛋白酶、STAT3、细胞周期蛋白、NF-κB、COX-2、MMP-9、VEGF/R 等)的相互作用以及对广泛的细胞内信号转导途径的调节。这些数据为进一步开展体内研究和临床试验提供了良好的基础。除了努力克服植物代谢物通常具有的低生物利用度问题外,布替丁还可以被视为未来安全且更有效的癌症药物的潜在先导化合物。

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