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Abstract
Fucoxanthin (Fx) is a carotenoid derived from marine organisms that exhibits anticancer activities. However, its role as a potential drug adjuvant in breast cancer (BC) treatment is still poorly explored. Firstly, this study investigated the cytotoxic effects of Fx alone and combined with doxorubicin (Dox) and cisplatin (Cis) on a panel of 2D-cultured BC cell lines (MCF7, SKBR3 and MDA-MB-231) and one non-tumoral cell line (MCF12A). Fucoxanthin induced cytotoxicity against all the cell lines and potentiated Dox cytotoxic effects towards the SKBR3 and MDA-MB-231 cells. The combination triggering the highest cytotoxicity (Fx 10 µM + Dox 1 µM in MDA-MB-231) additionally showed significant induction of cell death and genotoxic effects, relative to control. In sequence, the same combination was tested on 3D cultures using a multi-endpoint approach involving bioactivity assays and microscopy techniques. Similar to 2D cultures, the combination of Fx and Dox showed higher cytotoxic effects on 3D cultures compared to the isolated compounds. Furthermore, this combination increased the number of apoptotic cells, decreased cell proliferation, and caused structural and ultrastructural damages on the 3D models. Overall, our findings suggest Fx has potential to become an adjuvant for Dox chemotherapy regimens in BC treatment.
Highlights
Nature has always been a source of active substances for drug development, and despite the advances in synthetic biology, most of the currently approved medicines are based on natural products [1,2]
In line with the one-way ANOVA analysis detecting differences between groups in the MDA-MB-231 and MCF7 cell lines, the Holm–Bonferroni corrected t-tests comparing only the Fx 10 μM with control (p < 0.05 and p < 0.001, respectively) indicated that Fx induced statistically significant cytotoxicity in those cells
The combination of Fx (1 or 10 μM) with Cis 20 μMC2.de3l.lePCchuraletsuaer3se—es dEffceectlslofvFixabCoilmitbyineidnwirtehlDaotxioonn Cteoll DtheaethcaondnDtrNoAl.DMamoargee oinv2eDr, cells treated with Dox alone atT1heμeMffecat sofwtheellsealescwteditchomthbeincatoiomnbainndarteisopnecstiFvexi1so0laμteMd c+omDpoouxn0d.s1oμn Mthe induction of cell death in MDA-MB-231 cells was evaluated by the nuclear condensation assay after 72 h of exposure
Summary
Nature has always been a source of active substances for drug development, and despite the advances in synthetic biology, most of the currently approved medicines are based on natural products [1,2]. More than 60% of the anticancer drugs used in clinical practice are derived from natural sources, including the well-known chemotherapeutics doxorubicin (Dox), paclitaxel, vincristine and vinblastine [1,3]. Marine organisms yield a wide variety of bioactive compounds with unique properties and promising potential for developing new anticancer drugs [6,7]. Seaweeds (or macroalgae) bear a high content of phytochemicals (e.g., carotenoids, polyphenolic compounds and polysaccharides) with promising chemopreventive and chemotherapeutic properties towards several types of cancer, namely breast cancer (BC) [10]. Some studies have been pointing out the benefits of dietary seaweed consumption on the prevention of BC [12,13]
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