Effect of Folate Deficiency on the Sensitivity of Colon Cancer Cells to 5-Fluorouracil Based Chemotherapy

Folate is an essential cofactor in one-carbon transfer reactions including nucleotide biosynthesis, thereby playing an important role in DNA replication and repair. In cancer cells, folate depletion interrupts DNA synthesis, thereby causing cancer cell death. This has been the basis for chemotherapy using antifolates and 5-fluorouracil (5FU). We determined the effect of folate deficiency on the sensitivity of colon cancer cells to 5FU in a well established in vitro model of folate deficiency. Folate deficient cells had lower intracellular folate concentrations, had functional evidence of intracellular folate depletion, proliferated less, and had increased chemosensitivity to 5FU with and without Leucovorin. These data suggest that folate deficiency significantly enhances the sensitivity of colon cancer cells to 5FU based chemotherapy via changes in intracellular folate. Dietary or other strategies to deplete intracellular folate concentrations in colon cancer cells to enhance chemosensitivity to 5FU are worthy of further investigation.MAS