Abstract Breast cancer is the most commonly occurring cancer in women worldwide and is the second most common cancer among women in the United States. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer and accounts for about 10-15% of all breast cancers. TNBC is mainly found in Caucasian and African American women. The tumor microenvironment promotes tumor initiation and progression, preceding invasive metastasis, increased cell growth, and angiogenesis. Therefore, the inhibition of these processes may reduce breast cancer development. Several dietary natural products show the ability to ameliorate the aggressiveness of breast cancer, leading to the inhibition of proliferation and angiogenesis, induction of apoptosis, and reduction of breast cancer progression and tumor development. PURPOSE: In the current study, the pharmacological effect of the natural compound fucoxanthin, a xanthophyll subset of carotenoids in brown macroalgae, is investigated in genetically different MDA-MB-231 (Caucasian) and MDA-MB-468 (African American) TNBC cell lines. METHODS: Cytotoxic and cell growth assays, angiogenic arrays, RT-PCR, apoptotic, and migration assays were performed. RESULTS: Fucoxanthin (1.56 - 300 µM) decreased cell viability in a dose and time-response manner in both cell lines, showing a higher potency in MDA-MB-468 cells. Fucoxanthin presented anti-proliferative effects in lower concentrations in MDA-MB-468 compared to MDA-MB-231 cells after 48 h and 72 h. Angiogenesis studies showed that fucoxanthin (6.25 µM) downregulates VEGF-A and VEGF-C expression in TNF-α-stimulated (50 ng/ml) MDA-MB-231 cells, but not in MDA-MB-468 cells in the transcription and protein levels. Fucoxanthin induced apoptosis in MDA-MB-231 cells but did not affect MDA-MB-468 cells. Additionally, fucoxanthin inhibited migration and invasion in both cell lines, showing a higher percentage of the inhibition of migrated cells in MDA-MB-468 cells after 72 h. CONCLUSION: Fucoxanthin may be a promising candidate for breast cancer therapy by targeting VEGF-A, and VEGF-C, decreasing cell proliferation, inducing apoptosis, and inhibiting cell migration and invasion. Citation Format: Shade' Ahmed, Patricia Mendonca, Samia Messeha, Ramesh Badisa, Karam F. Soliman. Fucoxanthin anti-tumor effects on the proliferation, angiogenesis, apoptosis, and migration of triple-negative breast cancer cells [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C021.