The Algal Antioxidant Carotenoid Diatoxanthin as a Modulator of Inflammation and Angiogenesis in Triple-Negative Breast Cancer Cells

Algal carotenoids play a promising role in handling chronic disease due to their diverse bioactive properties, including anti-inflammatory, antioxidant, and anticancer effects. This study assesses the activity of the antioxidant xanthophyll diatoxanthin (Dt), derived from marine diatoms, against triple-negative breast cancer (TNBC) cells using in vitro models, gene expression evaluation and explorings its role in potentiating the cytotoxic effect of chemotherapy. Dt exhibited selective activity against MDA-MB-231 and BT-549 TNBC cells and when combined with doxorubicin synergistically enhanced anti-tumor efficacy in both TNBC cell lines by further reducing cell viability. Dt also exerted its activity in inhibiting migration, chemotaxis, and suppressing 3D-tumor spheroid growth, and downregulating angiogenesis-related genes. Notably, secretome analysis revealed that Dt-induced changes in inflammatory, oxidative and angiogenic mediators, highlighting its ability to modulate the TNBC microenvironment. Dt also downregulated key pro-survival, proangiogenic and pro-tumorigenic genes in both TNBC cell lines, supporting its role in disrupting oncogenic pathways. Angiogenesis-related genes were significantly reduced. Dt also decreased the expression of angiogenic mediators in HUVEC cells, supporting Dt’s role in inhibiting tumor vascularization. Results on gene expression regulation were confirmed by RNAseq analysis. These findings pose Dt as a multifaceted candidate for contrasting TNBC, capable of targeting inflammation, angiogenesis, tumor cell growhth, and cell migration. Given its selective activity against TNBC cells, ability to enhance chemotherapy efficacy, and modulation of the tumor microenvironment, Dt holds promise as complementary drug for cancer prevention and interception. Future studies should focus on validating these effects in vivo and exploring Dt’s potential in combinatorial treatment strategies for cancer.