Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, Prague 6, Czech Republic.
Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 3, Prague 6, Czech Republic.
Toxins (Basel). 2021 May 11;13(5):344. doi: 10.3390/toxins13050344.
Cardiac glycosides (CGs), toxins well-known for numerous human and cattle poisoning, are natural compounds, the biosynthesis of which occurs in various plants and animals as a self-protective mechanism to prevent grazing and predation. Interestingly, some insect species can take advantage of the CG's toxicity and by absorbing them, they are also protected from predation. The mechanism of action of CG's toxicity is inhibition of Na/K-ATPase (the sodium-potassium pump, NKA), which disrupts the ionic homeostasis leading to elevated Ca concentration resulting in cell death. Thus, NKA serves as a molecular target for CGs (although it is not the only one) and even though CGs are toxic for humans and some animals, they can also be used as remedies for various diseases, such as cardiovascular ones, and possibly cancer. Although the anticancer mechanism of CGs has not been fully elucidated, yet, it is thought to be connected with the second role of NKA being a receptor that can induce several cell signaling cascades and even serve as a growth factor and, thus, inhibit cancer cell proliferation at low nontoxic concentrations. These growth inhibitory effects are often observed only in cancer cells, thereby, offering a possibility for CGs to be repositioned for cancer treatment serving not only as chemotherapeutic agents but also as immunogenic cell death triggers. Therefore, here, we report on CG's chemical structures, production optimization, and biological activity with possible use in cancer therapy, as well as, discuss their antiviral potential which was discovered quite recently. Special attention has been devoted to digitoxin, digoxin, and ouabain.
强心苷（CGs）是一种天然化合物，以多种植物和动物为原料，是一种众所周知的、能导致人和牛中毒的毒素，其生物合成是作为一种自我保护机制，以防止被啃食和捕食。有趣的是，一些昆虫物种可以利用 CG 的毒性，通过吸收 CG 来保护自己免受捕食。CG 毒性的作用机制是抑制 Na/K-ATP 酶（钠钾泵，NKA），这会破坏离子平衡，导致 Ca 浓度升高，从而导致细胞死亡。因此，NKA 是 CGs 的分子靶标（尽管它不是唯一的靶标），尽管 CGs 对人和一些动物有毒，但它们也可以用作治疗各种疾病的药物，如心血管疾病，甚至癌症。虽然 CGs 的抗癌机制尚未完全阐明，但它被认为与 NKA 的第二个作用有关，即作为一种受体，可以诱导几种细胞信号级联反应，甚至作为一种生长因子，从而在低非毒性浓度下抑制癌细胞增殖。这些生长抑制作用通常仅在癌细胞中观察到，从而为 CGs 重新定位用于癌症治疗提供了可能性，不仅作为化疗药物，而且作为免疫原性细胞死亡的触发剂。因此，在这里，我们报告了 CG 的化学结构、生产优化和生物活性，以及它们在癌症治疗中的可能应用，并讨论了它们最近才被发现的抗病毒潜力。特别关注的是洋地黄毒苷、地高辛和哇巴因。
