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

Costa, Luciana Amaral de Mascena; Harmon, Ashlyn C.; Teixeira, Álvaro Aguiar Coelho; Lima, Filipe Cássio Silva de; Araújo, Silvany de Sousa; Piero, Fábio Del; Souza, Helivaldo Diógenes da Silva; Filho, Petrônio Filgueiras de Athayde; Alves, Severino; Maia, Maria de Mascena Diniz; Wischral, Áurea; Filho, Manoel Adrião Gomes; Mathis, J. Michael

doi:10.1177/1178223420913330

Cited by 2 publications

(1 citation statement)

References 54 publications

(66 reference statements)

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“…In our previous study, a 1,3-thiazolium-5-thiolate derivative of a mesoionic compound, MIH 2.4Bl was synthesized (14), and its potential selective anti-cancer properties were assessed using a panel of breast cancer cell lines and cells derived from normal human breast lineage. Treatment with MIH 2.4Bl inhibited growth of most of the breast cancer cell lines tested compared with normal human mammary epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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 IC 50 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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Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Theranostics Using MCM-41-Based Mesoporous Silica Nanoparticles: Integrating Magnetic Resonance Imaging and Novel Chemotherapy for Breast Cancer Treatment

Pires,

Shuchi,

Tostes

et al. 2024

IJMS

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Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3⁺-MIH and its potential to enhance breast cancer management.

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

Cited by 2 publications

References 54 publications

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

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

Theranostics Using MCM-41-Based Mesoporous Silica Nanoparticles: Integrating Magnetic Resonance Imaging and Novel Chemotherapy for Breast Cancer Treatment

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