Recombinant Arginine Deiminase from Levilactobacillus brevis Inhibits the Growth of Stomach Cancer Cells, Possibly by Activating the Intrinsic Apoptosis Pathway

• Published in: International journal of molecular sciences Vol. 25; no. 8; p. 4163
• Main Authors: Mendoza, Remilyn M, Song, Ji Hoon, Jung, Yong Tae, Paik, Hyun-Dong, Park, Young-Seo, Kang, Dae-Kyung
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09-04-2024
• Subjects: Amino acids; anticancer; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; arginine deiminase; Cancer therapies; Cell cycle; Cell death; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Flow cytometry; Gastric cancer; Genes; genome analysis; Genomes; Humans; Hydrolases - genetics; Hydrolases - metabolism; Hydrolases - pharmacology; lactic acid bacteria; Levilactobacillus brevis - enzymology; Levilactobacillus brevis - genetics; Liver cancer; Metabolism; Metabolites; Molecular weight; Proteins; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; Signal Transduction - drug effects; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; arginine deiminase; apoptosis; lactic acid bacteria; genome analysis; anticancer
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25084163

The anticancer potential of
KU15176 against the stomach cancer cell line AGS has been reported previously. In this study, we aimed to analyze the genome of
KU15176 and identify key genes that may have potential anticancer properties. Among potential anticancer molecules, the role of arginine deiminase (ADI) in conferring an antiproliferative functionality was confirmed. In vitro assay against AGS cell line confirmed that recombinant ADI from
KU15176 (ADI_br, 5 µg/mL), overexpressed in
BL21 (DE3), exerted an inhibitory effect on AGS cell growth, resulting in a 65.32% reduction in cell viability. Moreover, the expression of apoptosis-related genes, such as
,
,
-7, and
-3, as well as the activity of caspase-9 in ADI_br-treated AGS cells, was higher than those in untreated (culture medium-only) cells. The cell-scattering behavior of ADI_br-treated cells showed characteristics of apoptosis. Flow cytometry analyses of AGS cells treated with ADI_br for 24 and 28 h revealed apoptotic rates of 11.87 and 24.09, respectively, indicating the progression of apoptosis in AGS cells after ADI_br treatment. This study highlights the potential of ADI_br as an effective enzyme for anticancer applications.