Methionine gamma lyase from Clostridium sporogenes increases the anticancer effect of doxorubicin in A549 cells and human cancer xenografts

Abstract

The anti-cancer efficacy of methionine γ-lyase (MGL) from Clostridium sporogenes (C. sporogenes) is described. MGL was active against cancer models in vitro and in vivo. The calculated EC50 values for MGL were 4.4 U/ml for A549, 7.5 U/ml for SK-BR3, 2.4 U/ml for SKOV3, and 0.4 U/ml for MCF7 cells. The combination of doxorubicin (DOX) and MGL was more effective for A549 human lung cancer growth inhibition than either agent alone in vitro and in vivo. MGL reduced the EC50 of doxorubicin from 35.9 μg/mL to 0.01-0.265 μg/mL. The growth inhibitory effect of DOX + MGL on A549 xenografts in vivo was reflective of the results obtained in vitro. The inhibition rate of tumor growth in the combined arm was 57%, significantly higher than that in the doxorubicin (p = 0.033)-alone arm.

MGL S3 Chimeric Enzyme Drives Apoptotic Death of EGFR-Dependent Cancer Cells through ERK Downregulation

“…Given that the response of cancer cells to bacterial-derived and genetically engineered MGL is not defined by their origin [ 2 , 8 , 24 ], we have assessed the sensitivity of four human cancer cell lines (H1299, SH-SY5Y, SK-BR-3, and HCT116) to MGL tetani and novel recombinant protein MGL S3, obtained by genetic engineering, consisting of MGL and EGF-like peptide.…”

“…Notably, the cytotoxicity of methionine gamma lyase against normal skin fibroblasts was twice as low compared to the most MGL-unsensitive H1993 lung adenocarcinoma cell line [ 8 ]. In addition, in our previous work we showed the good tolerability of MGL from Clostridium sporogenes in a mouse model [ 24 ].…”

“…In addition, recombinant fusion proteins consisting of MGL linked to the different peptides are promising for the selective and effective elimination of cancer cells in vitro and in vivo [ 21 , 22 ]. Although methionine deprivation alone possesses significant antitumor activity, it also exerts significant synergistic effects on the in vivo reduction of tumor growth when combined with widely used cancer therapies, including the chemotherapeutic drug 5-fluorouracil for colorectal cancer [ 23 ] and doxorubicin and cisplatin for lung cancer [ 24 ].…”

Anti-Inflammatory Activity of Soluble Epoxide Hydrolase Inhibitors Based on Selenoureas Bearing an Adamantane Moiety

“…The error in the luminescence measurements was calculated using the standard deviation equation based on 3 repeats, its values on the graphs are shown with error bars. EC 50 concentrations were determined using Combenefit software [45,46].…”

Recent advances in human respiratory epithelium models for drug discovery

“…A549 cells have been recently utilised to determine the anti-inflammatory properties of novel plant-based compounds (Henz Ryen et al, 2020). The carcinomic nature of A549 cells have directed their use for compound efficacy testing of novel anti-cancer treatments (Pokrovsky et al, 2019).…”