Breast cancer (BC) accounts for the most cancer-related deaths amongst women worldwide, implying an urgent need of finding new drugs more effective than those currently in use [1, 2]. Fucoxanthin (Fx) is a marine carotenoid derived from brown seaweed that has been showing antitumor effects on different cancer cell lines, mainly in 2D models [3]. However, 3D culture models have a better predictive capacity of in vivo cellular responses against cytotoxic compounds [4]. This study aimed to evaluate the potential anticancer effects of Fx versus Doxorubicin (Dox) (a conventional anticancer drug) in a panel of three BC cell lines, representative of different molecular subtypes (MCF-7, SKBR3 and MDA-MB-231), and in a non-tumoral BC cell line (MCF-12A), cultured under 2D and 3D conditions. Effects on cell viability, death, proliferation and DNA damage were targeted. Results from the 2D cultures showed that Dox and Fx caused cytotoxicity on all the cell lines. Cytotoxic activity of Dox involved mechanisms of cell death induction (in MCF-12A cells) and genotoxicity (in MDA-MB-231 cells), contrarily to Fx, where neither cell death nor genotoxic mechanisms were detected. Under 3D conditions, cells were less responsive to Dox and Fx, compared to 2D cultures. Antiproliferative effects were solely registered in SKBR3 cells exposed to Dox and Fx, and in MCF-12A cells exposed to Dox. The in vitro data revealed that the Fx may be a potential anticancer agent against BC cells, with differential effects according to the cell subtype. The data warrants further studies on the underlying anticancer mechanisms.

Acknowledgments: We thank the fundamental financial support of the ICBAS of the UPorto, namely via its Laboratory of Histology and Embryology and Master Program in Environmental Contamination and Toxicology. This research was also partially supported by the Strategic Funding UID/Multi/04423/2019 through national funds provided by FCT and ERDF, in the framework of the program PT2020.

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