Cytotoxic Activity of the Mesoionic Compound MIH 2.4Bl in Breast Cancer Cell Lines




Amaral de Mascena Costa, Luciana
Harmon, Ashlyn C.
Aguiar Coelho Teixeira, Alvaro
Cassio Silva de Lima, Filipe
de Sousa Araujo, Silvany
Del Piero, Fabio
Diogenes da Silva Souza, Helivaldo
Filgueiras de Athayde Filho, Petronio
Alves Junior, Severino
de Mascena Diniz Maia, Maria


0000-0001-5528-5195 (Mathis, J. Michael)

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Sage Publications


In this work, we report the synthesis of a new 1,3-thiazolium-5-thiolate derivative of a mesoionic compound (MIH 2.4Bl) and the characterization of its selective cytotoxicity on a panel of breast cancer cells lines. The cytotoxic effect of MIH 2.4Bl on breast cancer cell lines was determined by XTT and crystal violet assays, flow cytometry analysis, electron microscopy characterization, and terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) apoptosis assays. As determined using XTT cell growth and survival assays, MIH 2.4Bl exhibited growth inhibition activity on most breast cancer cell lines tested, compared with normal human mammary epithelial cells. Three breast cancer cell lines (MCF-7, T-47D, and ZR-75-1) showed a more potent sensitivity index to growth inhibition by MIH 2.4Bl than the other breast cancer cell lines. Interestingly, these 3 cell lines were derived from tumors of Luminal A origin and have ER (estrogen receptor), PR (progesterone receptor), and HER2 (human epidermal growth factor receptor 2) positive expression. Additional analysis of cytotoxicity mediated by MIH 2.4Bl was performed using the MCF-7 cell line. MCF-7 cells displayed both time- and dose-dependent decreases in cell growth and survival, with a maximum cytotoxic effect observed at 72 and 96 hours. The MCF-7 cells were also characterized for cell cycle changes upon treatment with MIH 2.4Bl. Using flow cytometry analysis of cell cycle distribution, a treatment-dependent effect was observed; treatment of cells with MIH 2.4Bl increased the G2/M population to 34.2% compared with 0.1% in untreated (control) cells. Ultrastructural analysis of MFC-7 cells treated with MIH 2.4Bl at 2 different concentrations (37.5 and 75 muM) was performed by transmission electron microscopy. Cells treated with 37.5 muM MIH 2.4Bl showed morphologic changes beginning at 6 hours after treatment, while cells treated with 75 muM showed changes beginning at 3 hours after treatment. These changes were characterized by an alteration of nuclear morphology and mitochondrial degeneration consistent with apoptotic cell death. Results of a TUNEL assay performed on cells treated for 96 hours with MIH 2.4Bl supported the observation of apoptosis. Together, these results suggest that MIH 2.4Bl is a promising candidate for treating breast cancer and support further in vitro and in vivo investigation.



Amaral de Mascena Costa, L., Harmon, A. C., Aguiar Coelho Teixeira, A., Cássio Silva de Lima, F., de Sousa Araújo, S., Del Piero, F., Diógenes da Silva Souza, H., Filgueiras de Athayde Filho, P., Alves Junior, S., de Mascena Diniz Maia, M., Wischral, A., Adrião Gomes Filho, M., & Mathis, J. M. (2020). Cytotoxic Activity of the Mesoionic Compound MIH 2.4Bl in Breast Cancer Cell Lines. Breast cancer : basic and clinical research, 14, 1178223420913330.


© The Author(s) 2020.


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