MnTnHex-2-PyP5+ Displays Anticancer Properties and Enhances Cisplatin Effects in Non-Small Cell Lung Cancer Cells

Abstract

The manganese(III) porphyrin MnTnHex-2-PyP5+ (MnTnHex) is a potent superoxide dismutase mimic and modulator of redox-based transcriptional activity that has been studied in the context of different human disease models, including cancer. Nevertheless, for lung cancer, hardly any information is available. Thus, the present work aims to fill this gap and reports the effects of MnTnHex in non-small cell lung cancer (NSCLC) cells, more specifically, A549 and H1975 cells, in vitro. Both cell lines were initially characterized in terms of innate levels of catalase, glutathione peroxidase 1, and peroxiredoxins 1 and 2. To assess the effect of MnTnHex in NSCLC, alone or in combination with cisplatin, endpoints related to the cell viability, cell cycle distribution, cell motility, and characterization of the volatile carbonyl compounds (VCCs) generated in the extracellular medium (i.e., exometabolome) were addressed. The results show that MnTnHex as a single drug markedly reduced the viability of both NSCLC cell lines, with some IC50 values reaching sub-micromolar levels. This redox-active drug also altered the cell cycle distribution, induced cell death, and increased the cytotoxicity pattern of cisplatin. MnTnHex also reduced collective cell migration. Finally, the metabolomics study revealed an increase in the levels of a few VCCs associated with oxidative stress in MnTnHex-treated cells. Altogether these results suggest the therapeutic potential of MnTnHex to be further explored, either alone or in combination therapy with cisplatin, in NSCLC.

Biogenic Synthesis of Cu-Mn Bimetallic Nanoparticles Using Pumpkin Seeds Extract and Their Characterization and Anticancer Efficacy

“…The anti-migratory effects were more evident/noticeable at the highest tested concentrations of CMBNPs and at longer treatment durations. Several studies also reported different nanoformulations potential abilities to inhibit wound closure and cellular migration in various cancer cell lines [ 22 , 33 , 34 ].…”

Unveiling Novel ERCC1–XPF Complex Inhibitors: Bridging the Gap from In Silico Exploration to Experimental Design

“…To select the best NSCLC cell model to study the putative inhibitors, a characterization of the expression of the ERCC1 and ERCC4 (XPF) genes in all cell lines was performed by using quantitative reverse transcription PCR (qRT-PCR), following a previously described protocol [71]. Total RNA was isolated from each cell line (1.0 × 10 6 cells/sample) using TRIzol™ Reagent (Invitrogen™, Waltham, MA, USA) and extracted according to the manufacturer's instructions.…”

Drug-induced oxidative stress in cancer treatments: Angel or devil?

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