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曲古抑菌素A的药理特性,聚焦抗癌潜力:全面综述

Pharmacological Properties of Trichostatin A, Focusing on the Anticancer Potential: A Comprehensive Review.

作者信息

Bouyahya Abdelhakim, El Omari Nasreddine, Bakha Mohamed, Aanniz Tarik, El Menyiy Naoual, El Hachlafi Naoufal, El Baaboua Aicha, El-Shazly Mohamed, Alshahrani Mohammed Merae, Al Awadh Ahmed Abdullah, Lee Learn-Han, Benali Taoufiq, Mubarak Mohammad S

机构信息

Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco.

Laboratory of Histology, Embryology, and Cytogenetic, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat 10100, Morocco.

出版信息

Pharmaceuticals (Basel). 2022 Oct 8;15(10):1235. doi: 10.3390/ph15101235.

Abstract

Trichostatin A (TSA), a natural derivative of dienohydroxamic acid derived from a fungal metabolite, exhibits various biological activities. It exerts antidiabetic activity and reverses high glucose levels caused by the downregulation of brain-derived neurotrophic factor (BDNF) expression in Schwann cells, anti-inflammatory activity by suppressing the expression of various cytokines, and significant antioxidant activity by suppressing oxidative stress through multiple mechanisms. Most importantly, TSA exhibits potent inhibitory activity against different types of cancer through different pathways. The anticancer activity of TSA appeared in many and investigations that involved various cell lines and animal models. Indeed, TSA exhibits anticancer properties alone or in combination with other drugs used in chemotherapy. It induces sensitivity of some human cancers toward chemotherapeutical drugs. TSA also exhibits its action on epigenetic modulators involved in cell transformation, and therefore it is considered an epidrug candidate for cancer therapy. Accordingly, this work presents a comprehensive review of the most recent developments in utilizing this natural compound for the prevention, management, and treatment of various diseases, including cancer, along with the multiple mechanisms of action. In addition, this review summarizes the most recent and relevant literature that deals with the use of TSA as a therapeutic agent against various diseases, emphasizing its anticancer potential and the anticancer molecular mechanisms. Moreover, TSA has not been involved in toxicological effects on normal cells. Furthermore, this work highlights the potential utilization of TSA as a complementary or alternative medicine for preventing and treating cancer, alone or in combination with other anticancer drugs.

摘要

曲古抑菌素A(TSA)是一种源自真菌代谢产物的二烯异羟肟酸天然衍生物,具有多种生物学活性。它具有抗糖尿病活性,可逆转雪旺细胞中脑源性神经营养因子(BDNF)表达下调导致的高血糖水平;具有抗炎活性,可通过抑制多种细胞因子的表达来实现;还具有显著的抗氧化活性,可通过多种机制抑制氧化应激。最重要的是,TSA通过不同途径对不同类型的癌症表现出强大的抑制活性。TSA的抗癌活性在许多涉及各种细胞系和动物模型的研究中都有体现。事实上,TSA单独或与化疗中使用的其他药物联合使用时都具有抗癌特性。它可诱导某些人类癌症对化疗药物产生敏感性。TSA还对参与细胞转化的表观遗传调节剂发挥作用,因此被认为是一种癌症治疗的表观遗传药物候选物。因此,这项工作全面综述了利用这种天然化合物预防、管理和治疗包括癌症在内的各种疾病的最新进展以及多种作用机制。此外,本综述总结了最近涉及将TSA用作治疗各种疾病的药物的相关文献,强调了其抗癌潜力和抗癌分子机制。此外,TSA尚未涉及对正常细胞的毒理学影响。此外,这项工作强调了TSA作为预防和治疗癌症的补充或替代药物单独或与其他抗癌药物联合使用的潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0c2/9612318/fd4ac750a9bb/pharmaceuticals-15-01235-g001.jpg

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