Anticancer effects of seaweed compounds fucoxanthin and phloroglucinol, alone and in combination with 5-fluorouracil in colon cells

ABSTRACT

Colorectal cancer therapy with 5-fluorouracil (5-Fu) frequently become ineffective due to resistance to this drug; and thus other effective compounds are essential for therapy. It is well-known marine brown seaweeds contain antioxidant compounds the carotenoid fucoxanthin (Fx) and polyphenolic compound phloroglucinol (Ph) which exerted diverse biological activities including antioxidant and anticancer. The aim of this study was to determine the anticancer activities of Fx or Ph alone as well as combination of each chemical with 5-Fu on two human colorectal cancer cell lines (HCT116 and HT29), with comparison to responses in a normal colon cell line (CCD-18Co). Effects of these compounds on cell viability, induction of DNA damage, and cell death were evaluated using MTT assay, comet assay, nuclear condensation assay, and Western blot. 5-Fu decreased cell viability in a concentration-dependent manner in HCT116 and HT29 cells but was not cytotoxic in CCD-18Co cells. 5-Fu induced DNA damage in HCT116 cells with induction of cell death, while no marked effects on DNA damage and cell death were observed in HT29 cells. Fx or Ph alone also reduced cell viability in both cancer cell lines but no apparent cytotoxic effect in CCD-18Co cells, except for Fx at 50 and 100 µM. Diminished cell viability was accompanied by induction of DNA damage (by Fx) and induction of cell death (by Ph). In combination with 5-Fu, Fx at 10 µM (in HCT116 and HT29 cells), and Ph at 300 µM (in HT29 cells) enhanced the cytotoxic effect of 5-Fu; however, no marked cytotoxicity was noted in CCD-18Co cells. Since Fx and Ph alone reduced cancer cell line viability without an effect on normal cells and when in combination enhanced the cytotoxic effect of 5-Fu only in colon cancer cells, these compounds seem promising as anticancer agents.

Funding

Gargiulo D. was supported by CAPES, Brazil. 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 also 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. Finally, we thank the financial aid provided by the Master of Marine Sciences—Marine Resources, of the Institute of Biomedical Sciences Abel Salazar, University of Porto.

Additional information

Funding

Gargiulo D. was supported by CAPES, Brazil. 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 also 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. Finally, we thank the financial aid provided by the Master of Marine Sciences—Marine Resources, of the Institute of Biomedical Sciences Abel Salazar, University of Porto.