Ferulic acid, a
hydroxycinnamic acid, is abundant in vegetables, grains, and medicinal plants. Emerging evidence suggests that
ferulic acid may exert beneficial effects against
colorectal cancer. However, the anticancer activity of
ferulic acid is relatively low, and its metabolism after
oral administration is largely unknown. In this study, mimicking the enteric environment, human intestinal microflora and commercial probiotics were used to metabolize
ferulic acid to its metabolites, and their anticancer activities were evaluated.
Ferulic acid can be biotransformed to
4-vinylguaiacol (2-methoxy-4-vinylphenol), and the contents of
ferulic acid and
4-vinylguaiacol in bio-transformed extracts were determined by high-performance liquid chromatography (HPLC). Using the
chemotherapy-sensitive cell line HCT-116 and the chemo-resistant cell line HT-29, the cell proliferation was determined by the modified
trichrome stain assay. The cell cycle and induction of apoptosis were assayed using flow cytometry. HPLC data showed that there was a marked transformation from
ferulic acid to
4-vinylguaiacol, and the conversion rates of intestinal microflora and four probiotics were from 1.3 to 36.8%. Both
ferulic acid and
4-vinylguaiacol possessed dose- and time-related anticancer activities on the two cell lines, while
4-vinylguaiacol showed more potent effects than
ferulic acid. Interestingly,
4-vinylguaiacol exhibited significantly higher antiproliferative effects on the HT-29 cell line than that on HCT-116. The IC50 of the metabolite
4-vinylguaiacol on HT-29 cells was 350 μM, 3.7-fold higher than its parent compound. The potential of
cancer cell growth inhibition of
4-vinylguaiacol was mediated by cell cycle arrest at the G1 phase and induction of apoptosis. Data from this study indicate that the
oral administration of
ferulic acid offers a promising approach to increase its anticancer activity through gut microbial conversion to
4-vinylguaiacol, and the biotransformation could also be achieved by selected commercial probiotics.
4-Vinylguaiacol is a potential anticancer metabolite from
ferulic acid for
chemotherapy-resistant
colon cancer cells.