Recombinant Methioninase Selectively Eliminates Cancer Cells Co-cultured With Normal Fibroblasts Indicating the High-Precision Efficacy of Targeting Methionine Addiction of Cancer

Background/Aim: Methionine addiction is a fundamental and general hallmark of cancer and is targeted by methionine restriction. The aim of the present study was to examine whether methionine restriction can eliminate cancer cells co-cultured with normal cells that remain healthy. Materials and Methods: The IC50 for recombinant methioninase (rMETase) was determined for HC116 colon-cancer cells using the WST-8 viability assay. HCT-116 cells and Hs27 human normal skin fibroblasts were co-cultured and treated with rMETase at the IC50 concentration for HCT-116 cells. Cell morphology and viability were monitored over 16 days via phase-contrast microscopy. Results: The IC50 for rMETase was 0.46 U/ml for HCT-116 cancer cells. In the untreated control co-cultures, the HCT-116 colon cancer cells overgrew Hs27 normal fibroblasts from day 2. In contrast, rMETase-treated cultures showed elimination of HCT-116 cells by day 8, while Hs27 fibroblasts remained viable and proliferative throughout the experiment. Conclusion: The differential sensitivity of cancer and normal cells to rMETase at 0.46 U/ml was so extensive that cancer cells were essentially eliminated from the co-cultures while the normal cells remained viable and proliferating. The difference in sensitivity of normal and cancer cells growing together suggests that rMETase selectively and precisely targets methionine addiction of cancer and can be a safe and effective clinical anti-cancer agent.