Possible Interaction: Fluorouracil and Methionine

“Since MET deprivation can individually potentiate the different chemotherapeutic agents used in the 48-hour combined regimen of 5-FU , leucovorin and oxaliplatin (FOLFOX) regimen, we initiated a feasibility study associating dietary MET restriction with the FOLFOX regimen in patients with metastatic colorectal cancer.”

“Thus, methionine depletion by rMETase potentiates the antitumor efficacy of 5-FU.”

“ MET depletion enhanced the antitumor activity of 5-FU by approximately two-fold with statistical significance of p < 0.05.”

“Furthermore, western blot analysis revealed that both NK4 and 5-FU were inhibitors for HGF-induced phosphorylation of Met , but they may be independent factors.”

“These results suggest that synergy between methionine restriction and 5-fluorouracil is attributable to multiple factors, including depletion of reduced folates, selective inhibition of TS, and creation of an imbalanced nucleotide pool.”

“The combination of 3.7 × 10 −5 M PALA and 1 × 10 −6 M 5-FU produced 65–85 per cent inhibition of cell growth after continuous treatment for 13 days.”

“Moreover, this study explores the inhibition effect on gastric adenocarcinoma stem cell growth when combining 5-fluorouracil and methionine enzymes.”