Mechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF-7 breast cancer cells

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dc.creatorAmaral de Mascena Costa, Luciana
dc.creatorDebnath, Dipti
dc.creatorHarmon, Ashlyn C.
dc.creatorde Sousa Araujo, Silvany
dc.creatorDiogenes da Silva Souza, Helivaldo
dc.creatorFilgueiras de Athayde Filho, Petronio
dc.creatorWischral, Aurea
dc.creatorAdriao Gomes Filho, Manoel
dc.creatorMathis, J. Michael
dc.creator.orcid0000-0001-5528-5195 (Mathis, J. Michael)
dc.date.accessioned2022-10-14T16:48:29Z
dc.date.available2022-10-14T16:48:29Z
dc.date.issued2020-06-19
dc.description.abstractIn the present study, the cytotoxic effects of a 1,3-thiazolium-5-thiolate derivative of a mesoionic compound, MIH 2.4Bl, were assessed in the MCF-7 breast cancer cell line. The cytotoxic effects of MIH 2.4Bl were determined using a crystal violet assay. Using a dose-response curve, the IC50 value of MIH 2.4Bl was determined to be 45.8+/-0.8 microM. Additionally, the effects of MIH 2.4Bl on mitochondrial respiration were characterized using oxygen consumption rate analysis. Treating MCF-7 cells with increasing concentrations of MIH 2.4Bl resulted in a significant reduction in all mitochondrial respiratory parameters compared with the control cells, indicative of an overall decrease in mitochondrial membrane potential. The induction of autophagy by MIH 2.4Bl was also examined by measuring changes in the expression of protein markers of autophagy. As shown by western blot analysis, treatment of MCF-7 cells with MIH 2.4Bl resulted in increased protein expression levels of Beclin-1 and ATG5, as well as an increase in the microtubule-associated protein 1A/1B light chain 3B (LC3B)-II to LC3B-I ratio compared with the control cells. Microarray analysis of changes in gene expression following MIH 2.4Bl treatment demonstrated 3,659 genes exhibited a fold-change >/=2. Among these genes, 779 were up-regulated, and 2,880 were down-regulated in cells treated with MIH 2.4Bl compared with the control cells. Based on the identity of the transcripts and fold-change of expression, six genes were selected for verification by reverse transcription-quantitative (RT-q)PCR; activating transcription factor 3, acidic repeat-containing protein, heparin-binding EGF-like growth factor, regulator of G-protein signaling 2, Dickkopf WNT signaling pathway inhibitor 1 and adhesion molecule with Ig like domain 2. The results of RT-qPCR analysis of RNA isolated from control and MIH 2.4Bl treated cells were consistent with the expression changes identified by microarray analysis. Together, these results suggest that MIH 2.4Bl may be a promising candidate for treating breast cancer and warrants further in vitro and in vivo investigation.
dc.description.sponsorshipThe present study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, through an international scholarship awarded through the Science without Borders program (grant no. 88887.122971/2016-00), and through research bridge funding provided by the Department of Cellular Biology and Anatomy at LSU School of Veterinary Medicine.The present study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, through an international scholarship awarded through the Science without Borders program (grant no. 88887.122971/2016-00), and through research bridge funding provided by the Department of Cellular Biology and Anatomy at LSU School of Veterinary Medicine.
dc.identifier.citationde Mascena Costa, L. A., Debnath, D., Harmon, A. C., de Sousa Araújo, S., da Silva Souza, H. D., de Athayde Filho, P. F., Wischral, A., Adrião Gomes Filho, M., & Mathis, J. M. (2020). Mechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF-7 breast cancer cells. Oncology letters, 20(3), 2291-2301. https://doi.org/10.3892/ol.2020.11763
dc.identifier.issn1792-1074
dc.identifier.issue3
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31871
dc.identifier.volume20
dc.publisherSpandidos Publications
dc.relation.urihttps://doi.org/10.3892/ol.2020.11763
dc.rights.holder© de Mascena Costa et al.
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceOncology Letters
dc.subjectautophagy
dc.subjectbreast cancer
dc.subjectcancer therapy
dc.subjectchemotherapy
dc.subjectcytotoxicity
dc.subjectmesoionic compound
dc.subjectmitochondria
dc.titleMechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF-7 breast cancer cells
dc.typeArticle
dc.type.materialtext

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