Cytotoxic activity of the seaweed compound fucosterol, alone and in combination with 5-fluorouracil, in colon cells using 2D and 3D culturing

Colorectal cancer (CRC) is one of the most frequently occurring carcinomas which require effective therapies. Fucosterol is a sterol present in marine brown seaweeds with several biological activities. However, the influence of fucosterol in CRC remains to be determined. Thus, the aim of this study was to examine the anticancer activity of fucosterol alone and in combination with 5-fluorouracil (5-Fu) on two human CRC cell lines (HCT116 and HT29) and compared with cytotoxicity in one normal colon fibroblast cell line (CCD-18co) in monolayer (2D). The effect of fucosterol alone or in combination with 5-Fu was further assessed using HT29 multicellular spheroids (3D). Data demonstrated that fucosterol alone or combined with 5-Fu decreased cell viability in HT29 cells in 2D cultures without inducing cytotoxic in normal colon cells. The combination, fucosterol, and 5-Fu, also inhibited cell proliferation, clonogenic potential and cell migration without producing cell death in 2D. In multicellular spheroids, the combination fucosterol plus 5-Fu at the same concentrations used in 2D was not effective demonstrating that under the tested conditions the 3D model was more resistant than the 2D model. Taken together, these findings suggest that fucosterol might be a promising alternative to enhance the cytotoxic and anti-invasive actions of 5-Fu in colon cancer cells without consequent major adverse effects in normal cells. Our results also reinforce the need to include more complex 3D culture models in the initial stages of drug screening.