Potentiation of Cell Death and DNA damage through 5-Fluorouracil and Ferulic acid Coadministration in p53 Mutant HT-29 Cell Lines

Abstract

When the Mediterranean diet is set in focus, scientific studies report a strong statistical correlation between human nutrition, diet, and cancer incidence. Considering the anticancer effects of a fiber-rich diet, it is understood that the anticancer effect is not only due to the bulk cellulosic material load but also related to the increased bioavailability of cellulose-bound bioactive (anticancer) compounds released due to intestinal microfloral activities. Ferulic acid (FA) is one of the components found ubiquitously in the fiber fraction of plant food. Because of its effects on cancer cell viability and its association with a low incidence of cancer concerning a high-fiber diet, FA can be considered an anticancer agent. Here in this work, it was investigated whether FA can potentiate the effects of anticancer drugs at lower doses. For this, a general anticancer drug named 5-Fluorouracil (5-FU) was used, and potentiation tests were performed on two cancer cell lines, namely A2780 besides HT-29, which has the homozygous mutation for p53. The results are interpreted as follows: anticancer effect of 5-FU was readily potentiated with 200 µM of FA in both cancer cell lines, and DNA damage-induced with 5-FU was enhanced with co-administration of FA. When cell viability and DNA damage of A2780 and HT-29 lines are evaluated together, we think it is most probable that 5-FU and FA administered jointly show its anticancer effect, especially by strengthening the apoptosis pathway triggered by DNA damage. If it might be possible to uncover the mechanism that drove DNA damage mediated apoptosis in p53 mutant HT-29 cells in our work we may shed light on the treatment of chemotherapy-resistant cancer incidences.