Ciencias Químico Biológicas, Universidad de Sonora, Hermosillo, Sonora, México.
Escuela de Ciencias de la Salud, Universidad Autónoma de Baja California, Ensenada, Baja California, México.
PeerJ. 2022 Jun 2;10:e13524. doi: 10.7717/peerj.13524. eCollection 2022.
Na/K-ATPase is an essential transmembrane enzyme found in all mammalian cells with critical functions for cell ion homeostasis. The inhibition of this enzyme by several cardiotonic steroids (CTS) has been associated with the cytotoxic effect on cancer cell lines of phytochemicals such as ouabain and digitoxin. This study evaluated the inhibitory capacity of cardenolides calotropin and corotoxigenin 3-O-glucopyranoside (C3OG) from over the Na/K-ATPase activity and . The inhibitory assays showed that calotropin and C3OG decreased the Na/K-ATPase activity with IC values of 0.27 and 0.87 μM, respectively. Furthermore, the molecules presented an uncompetitive inhibition on Na/K-ATPase activity, with K values of 0.2 μM to calotropin and 0.5 μM to C3OG. Furthermore, the molecular modeling indicated that calotropin and C3OG might interact with the Thr and Gln residues, considered essential to the interaction with the Na/K-ATPase. Besides, these cardenolides can interact with amino acid residues such as Phe, Leu, and Ala, to establish hydrophobic interactions on the binding site. Considering the results, these provide novel evidence about the mechanism of action of cardenolides from , proposing that C3OG is a novel cardenolide that deserves further consideration for cellular antiproliferative assays and studies as an anticancer molecule.
钠钾-ATP 酶是一种存在于所有哺乳动物细胞中的重要跨膜酶，对于细胞离子稳态具有关键功能。几种强心甾体（CTS）对该酶的抑制作用与植物化学物质如哇巴因和地高辛对癌细胞系的细胞毒性作用有关。本研究评估了来自 的卡烯内酯 calotropin 和 corotoxigenin 3-O-葡萄糖苷（C3OG）对 Na/K-ATP 酶活性的抑制能力。抑制试验表明，calotropin 和 C3OG 分别以 0.27 和 0.87 μM 的 IC 值降低了 Na/K-ATP 酶的活性。此外，这些分子对 Na/K-ATP 酶活性表现出非竞争性抑制作用，calotropin 的 K 值为 0.2 μM，C3OG 的 K 值为 0.5 μM。此外，分子建模表明，calotropin 和 C3OG 可能与 Thr 和 Gln 残基相互作用，这些残基被认为对与 Na/K-ATP 酶的相互作用至关重要。此外，这些卡烯内酯可以与 Phe、Leu 和 Ala 等氨基酸残基相互作用，在结合部位建立疏水相互作用。考虑到这些结果，这为 中的卡烯内酯的作用机制提供了新的证据，提出 C3OG 是一种新型的卡烯内酯，值得进一步考虑用于细胞增殖抑制试验和 作为抗癌分子的研究。
