Calotropin and corotoxigenin 3-O-glucopyranoside from the desert milkweed Asclepias subulata inhibit the Na + /K + -ATPase activity.

Autor: Meneses-Sagrero SE; Ciencias Químico Biológicas, Universidad de Sonora, Hermosillo, Sonora, México., Rascón-Valenzuela LA; Ciencias Químico Biológicas, Universidad de Sonora, Hermosillo, Sonora, México., García-Ramos JC; Escuela de Ciencias de la Salud, Universidad Autónoma de Baja California, Ensenada, Baja California, México., Vilegas W; Instituto de Biociências, São Paulo State University, Sao Paulo, Brasil., Arvizu-Flores AA; Ciencias Químico Biológicas, Universidad de Sonora, Hermosillo, Sonora, México., Sotelo-Mundo RR; Laboratorio de Estructura Molecular, Centro de Investigación en Alimentación y Desarrollo AC, Hermosillo, Sonora, México., Robles-Zepeda RE; Ciencias Químico Biológicas, Universidad de Sonora, Hermosillo, Sonora, México.
Jazyk: angličtina
Zdroj: PeerJ [PeerJ] 2022 Jun 02; Vol. 10, pp. e13524. Date of Electronic Publication: 2022 Jun 02 (Print Publication: 2022).
DOI: 10.7717/peerj.13524
Abstrakt: 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 Asclepias subulata over the Na + /K + -ATPase activity in vitro and silico . The inhibitory assays showed that calotropin and C3OG decreased the Na + /K + -ATPase activity with IC 50 values of 0.27 and 0.87 μM, respectively. Furthermore, the molecules presented an uncompetitive inhibition on Na + /K + -ATPase activity, with K i 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 797 and Gln 111 residues, considered essential to the interaction with the Na + /K + -ATPase. Besides, these cardenolides can interact with amino acid residues such as Phe 783 , Leu 125 , and Ala 323 , to establish hydrophobic interactions on the binding site. Considering the results, these provide novel evidence about the mechanism of action of cardenolides from A. subulata , proposing that C3OG is a novel cardenolide that deserves further consideration for in vitro cellular antiproliferative assays and in vivo studies as an anticancer molecule.
Competing Interests: Rogerio R. Sotelo-Mundo is an Academic Editor for PeerJ.
(© 2022 Meneses-Sagrero et al.)
Databáze: MEDLINE
Externí odkaz: