New bufadienolides extracted from Rhinella marina inhibit Na,K-ATPase and induce apoptosis by activating caspases 3 and 9 in human breast and ovarian cancer cells

Publication date: Available online 6 September 2019Source: SteroidsAuthor(s): Israel José Pereira Garcia, Gisele Capanema de Oliveira, Jéssica Martins de Moura Valadares, Felipe Finger Banfi, Silmara Nunes Andrade, Túlio Resende Freitas, Evaldo dos Santos Monção Filho, Hérica de Lima Santos, Gerardo Magela Vieira Júnior, Mariana Helena Chaves, Domingos de Jesus Rodrigues, Bruno Antonio Marinho Sanchez, Fernando P. Varotti, Leandro Augusto BarbosaAbstractBufadienolide compounds have been used for growth inhibition and apoptosis induction in tumor cells. Those families of cardiotonic steroids can bind the Na,K-ATPase, causing its inhibition. The use of bufadienolides is widely described in the literature as an anticancer function. The aim of this study was to evaluate the effects of bufadienolides and alkaloid isolated from venom samples from R. marina on tumor cells. We performed cytotoxicity assay in MDA-MB-231and TOV-21G cells and evaluated the activity of Caspases (3 and 9), Na, K-ATPase, PMCA and SERCA. Four compounds were extrated from the venom of R. marina. The compound 1 showed higher cytotoxicity in MDA-MB-231cells. Compound 1 also showed activation of Caspase 3 and 9. This compound caused an inhibition of the activity and expression of Na, K-ATPase, and also showed activation of both caspase-9 and caspase-3 in MDA-MB-231 cells. We also observed that Compound 1 had a direct effect on some ATPases, such as Na, K-ATPase, PMCA and SERCA. Compound 1 was able to inh...
Source: Steroids - Category: Drugs & Pharmacology Source Type: research