l-methioninase as a selective anticancer agent: dose-dependent cytotoxicity and metastasis suppression in methionine-dependent tumor cells

L-methioninase (l-met), a methionine-degrading enzyme, has shown potential for anticancer therapy. many tumor tissues have a limited ability to produce methionine and depend on external sources; hence, these tumors can be targeted by methionine-based treatments. the present study was conducted to investigate the effects of l-met on cancer cells, particularly hepatocellular carcinoma (hepg2) and pancreatic carcinoma (panc-1), and to evaluate its viability as a therapeutic agent. various techniques, including ammonium sulfate precipitation, dialysis, ion-exchange chromatography, and gel filtration chromatography, were employed to purify the enzyme l-met. a cytotoxicity test was conducted against hepg2 and panc-1 cells (at 25-200 µg/ml concentrations), using the mtt to evaluate cell viability, total nuclear intensity (tni), and cell membrane permeability (cmp). statistical analysis was done using one-way anova and dunnett's multiple comparisons test to compare study groups. l-met displayed dose-dependent growth inhibition of the specified cell lines. the panc-1 cell line exhibited an ic50 of 64.68 µg/ml, indicating a higher sensitivity to l-met compared to wrl 68 normal cells, which had an ic50 of 214.0 µg/ml. regarding hepg2, an even lower ic₅₀ of 66.44 µg/ml was observed, further confirming the selective targeting of cancer cells by l-met. treatment with l-met at a 200 µg/ml concentration significantly decreased tni and cmp levels in both the panc-1 and hepg2 cell lines, indicating increased cytotoxicity and compromised membrane integrity. additionally, l-met reduced matrix metalloproteinase activities in both cancer cell lines, a critical factor in metastasis. our study demonstrates the dose-dependent cytotoxic effects of l-met on methionine-dependent tumor cells, specifically hepg2 and panc-1. these findings highlight the need for optimized l-met dosing strategies in cancer treatment, particularly for methionine-dependent malignancies, paving the way for its potential use in targeted cancer therapy.