Open Access

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

  • Authors:
    • Luciana Amaral de Mascena Costa
    • Dipti Debnath
    • Ashlyn C. Harmon
    • Silvany de Sousa Araújo
    • Helivaldo Diógenes da Silva Souza
    • Petrônio Filgueiras de Athayde Filho
    • Aurea Wischral
    • Manoel Adrião Gomes Filho
    • J. Michael Mathis
  • View Affiliations

  • Published online on: June 19, 2020     https://doi.org/10.3892/ol.2020.11763
  • Pages: 2291-2301
  • Copyright: © de Mascena Costa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In 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 µM. 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.

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September-2020
Volume 20 Issue 3

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Spandidos Publications style
de Mascena Costa LA, Debnath D, Harmon AC, de Sousa Araújo S, da Silva Souza HD, de Athayde Filho PF, Wischral A, Adrião Gomes Filho M and Mathis JM: Mechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF‑7 breast cancer cells. Oncol Lett 20: 2291-2301, 2020
APA
de Mascena Costa, L.A., Debnath, D., Harmon, A.C., de Sousa Araújo, S., da Silva Souza, H.D., de Athayde Filho, P.F. ... 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, 2291-2301. https://doi.org/10.3892/ol.2020.11763
MLA
de 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."Mechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF‑7 breast cancer cells". Oncology Letters 20.3 (2020): 2291-2301.
Chicago
de 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."Mechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF‑7 breast cancer cells". Oncology Letters 20, no. 3 (2020): 2291-2301. https://doi.org/10.3892/ol.2020.11763