Fucoxanthin Holds Potential to Become a Drug Adjuvant in Breast Cancer Treatment: Evidence from 2D and 3D Cell Cultures

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.

A Systematic Review on Marine Algae-Derived Fucoxanthin: An Update of Pharmacological Insights

“…Fucoxanthin causes epigenetic and transcriptomic reprogramming, which potentially contributes to the protection of TPA-induced JB6 cellular transformation skin cancer in an animal model [ 58 ]. Some reports also suggest that fucoxanthin can be used in combination with other chemotherapy agents to achieve the maximum benefit of chemotherapy [ 59 , 60 ]. The above preclinical evidence suggests that fucoxanthin might have the potential to curb one of the challenging diseases of our time to be considered as a novel therapeutic agent against cancer.…”

Fucoxanthin Is a Potential Therapeutic Agent for the Treatment of Breast Cancer

“…Konishi, Funahashi and their colleagues show an increase in DNA fragmentation in BC cells after Fx and Fxol treatments, indicating the anti-proliferative effects of Fx and Fxol. However, another study showed that Fx neither induces detectable cell death nor DNA damage in the BC cells [96]. Different experimental conditions may contribute to the discrepancies, such as the culture conditions, Fx concentrations, treatment protocols and the analytical methods for DNA damage and cell death.…”

“…The anti-proliferation effects of Fx and Fxol in BC cells have been explored by many researchers (Table 1). Numerous studies show that Fx and Fxol significantly reduce the cell viabilities of MCF7, SKBR3 and MDA-MB-231 cells in dose-and time-dependent manners [91][92][93][94][95][96]. Rwigemera reported that Fx and Fxol reduce the cell viability of MDA-MB-231 cells to a greater extent, while Fxol exhibits stronger anti-proliferation effects than Fx does.…”

“…These results demonstrated the synergistic effect of Fx in combination with DOX in inhibiting BC cell viability. Malhão also suggests Fx to be a potential drug adjuvant based on the cytotoxic results in 2D-and 3D-cultured BC cell models such as MCF7, SKBR3 and MDA-MB-231 cells with Fx alone or combined with Dox and cisplatin (Cis) [96]. Malhão also claims that the synergistic effects of this combination are more pronounced in the TNBC cells [96].…”

“…Malhão also suggests Fx to be a potential drug adjuvant based on the cytotoxic results in 2D-and 3D-cultured BC cell models such as MCF7, SKBR3 and MDA-MB-231 cells with Fx alone or combined with Dox and cisplatin (Cis) [96]. Malhão also claims that the synergistic effects of this combination are more pronounced in the TNBC cells [96]. In order to reveal the reversal effects of Fx in MDR, a study used adriamycin (DOX) resistance cell lines MCF-7/ADR to examine the effects of Fx in overcoming drug resistance [90].…”