Breast cancer is the second most diagnosed cause of death in women worldwide compared to other cancer types. Triple-negative breast cancer (TNBC) is the most aggressive subtype, constituting 15% of diagnosed breast cancers and predominantly found in African American and Caucasian Women. The tumor microenvironment is associated with increased angiogenesis, cell growth, invasive metastasis, and tumor growth progression. Many natural products have been reported to inhibit angiogenesis and slow breast cancer progression. The cytotoxic effect of the natural compound fucoxanthin, a xanthophyll found in the chloroplasts of brown macroalgae, is investigated. Fucoxanthin has been shown to induce G1 cell-cycle arrest and apoptosis in various cancer cell lines. Here we show that fucoxanthin affects proliferation and angiogenesis in MDA-MB-231 (Caucasian) and MDA-MB-468 (African American) TNBC cell lines, which are genetically different. The results demonstrate that fucoxanthin induces a decrease in cell viability (concentration range: 1.56 - 300 µM) in a dose-response manner in MDA-MB-231 and MDA-MB-468 cells, showing a higher potency in MDA-MB-468 cells compared to MDA-MB-231 cells after 24h. Fucoxanthin also showed anti-proliferative effects in lower concentrations in MDA-MB-468 cells compared to MDA-MB-231 cells after 48h and 72h. Moreover, angiogenesis studies showed that fucoxanthin (6.25 µM) downregulates the expression of VEGF-A and VEGF-C in TNF-α-stimulated (50 ng/ml) MDA-MB-231 cells, but not in MDA-MB-468 cells. The findings show that fucoxanthin may be a promising candidate for breast cancer therapy by targeting VEGF-A, VEGF-C, and reducing cell proliferation. Also, the data obtained provide evidence that genetically different cells may respond differently to fucoxanthin treatment.
Research reported in this project was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number U54 MD007582