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

ABSTRACT

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.

KEYWORDS:

• 5-Fu
• anticancer activity
• cytotoxicity
• colon cancer cell lines
• fucosterol
• spheroids

Conflict of interest

There are no conflicts of interest to report.

Acknowledgments

This research was partially supported by the Research Line NOVELMAR – Novel marine products with biotechnological applications, integrated into the Structured Program of R&D&I INNOVMAR – Innovation and Sustainability in the Management and Exploitation of Marine Resources (reference NORTE-01-0145-FEDER-000035), funded by the Northern Regional Operational Programme (NORTE2020) through the European Regional Development Fund (ERDF). The study was further supported by the ERDF, through the Competitiveness and Trade Expansion Program (COMPETE), and by national funds provided by the Foundation for Science and Technology (FCT), under the Strategic Funding UID/Multi/04423/2013. Alice Ramos was directly supported by the contract NOVELMAR/IA3/2016-041. At last, additional funding was provided by the Institute of Biomedical Sciences Abel Salazar, University of Porto, namely via its Master of Environmental Contamination and Toxicology.