Skip to main content

The Redox-Active Manganese(III) Porphyrin, MnTnBuOE-2-PyP5+, Impairs the Migration and Invasion of Non-Small Cell Lung Cancer Cells, Either Alone or Combined with Cisplatin.

Publication ,  Journal Article
Soares, RB; Manguinhas, R; Costa, JG; Saraiva, N; Gil, N; Rosell, R; Camões, SP; Batinic-Haberle, I; Spasojevic, I; Castro, M; Miranda, JP ...
Published in: Cancers (Basel)
July 27, 2023

Manganese(III) porphyrin MnTnBuOE-2-PyP5+ (MnBuOE, BMX-001) is a third-generation redox-active cationic substituted pyridylporphyrin-based drug with a good safety/toxicity profile that has been studied in several types of cancer. It is currently in four phase I/II clinical trials on patients suffering from glioma, head and neck cancer, anal squamous cell carcinoma and multiple brain metastases. There is yet an insufficient understanding of the impact of MnBuOE on lung cancer. Therefore, this study aims to fill this gap by demonstrating the effects of MnBuOE on non-small cell lung cancer (NSCLC) A549 and H1975 cell lines. The cytotoxicity of MnBuOE alone or combined with cisplatin was evaluated by crystal violet (CV) and/or 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-Tetrazolium (MTS) reduction assays. Intracellular ROS levels were assessed using two fluorescent probes. Furthermore, the impact of MnBuOE alone or in combination with cisplatin on collective cell migration, individual chemotactic migration and chemoinvasion was assessed using the wound-healing and transwell assays. The expression of genes related to migration and invasion was assessed through RT-qPCR. While MnBuOE alone decreased H1975 cell viability at high concentrations, when combined with cisplatin it markedly reduced the viability of the more invasive H1975 cell line but not of A549 cell line. However, MnBuOE alone significantly decreased the migration of both cell lines. The anti-migratory effect was more pronounced when MnBuOE was combined with cisplatin. Finally, MnBuOE alone or combined with cisplatin significantly reduced cell invasion. MnBuOE alone or combined with cisplatin downregulated MMP2, MMP9, VIM, EGFR and VEGFA and upregulated CDH1 in both cell lines. Overall, our data demonstrate the anti-metastatic potential of MnBuOE for the treatment of NSCLC.

Duke Scholars

Published In

Cancers (Basel)

DOI

ISSN

2072-6694

Publication Date

July 27, 2023

Volume

15

Issue

15

Location

Switzerland

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Soares, R. B., Manguinhas, R., Costa, J. G., Saraiva, N., Gil, N., Rosell, R., … Oliveira, N. G. (2023). The Redox-Active Manganese(III) Porphyrin, MnTnBuOE-2-PyP5+, Impairs the Migration and Invasion of Non-Small Cell Lung Cancer Cells, Either Alone or Combined with Cisplatin. Cancers (Basel), 15(15). https://doi.org/10.3390/cancers15153814
Soares, Rita B., Rita Manguinhas, João G. Costa, Nuno Saraiva, Nuno Gil, Rafael Rosell, Sérgio P. Camões, et al. “The Redox-Active Manganese(III) Porphyrin, MnTnBuOE-2-PyP5+, Impairs the Migration and Invasion of Non-Small Cell Lung Cancer Cells, Either Alone or Combined with Cisplatin.Cancers (Basel) 15, no. 15 (July 27, 2023). https://doi.org/10.3390/cancers15153814.
Soares RB, Manguinhas R, Costa JG, Saraiva N, Gil N, Rosell R, Camões SP, Batinic-Haberle I, Spasojevic I, Castro M, Miranda JP, Guedes de Pinho P, Fernandes AS, Oliveira NG. The Redox-Active Manganese(III) Porphyrin, MnTnBuOE-2-PyP5+, Impairs the Migration and Invasion of Non-Small Cell Lung Cancer Cells, Either Alone or Combined with Cisplatin. Cancers (Basel). 2023 Jul 27;15(15).

Published In

Cancers (Basel)

DOI

ISSN

2072-6694

Publication Date

July 27, 2023

Volume

15

Issue

15

Location

Switzerland

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis