Noni ( <i>Morinda citrifolia</i> L.) Fermented Juice Inhibits Tumor Progression of Breast Cancer Angiogenesis Through Suppressing NF‐κB Signaling

ABSTRACT Angiogenesis plays a crucial role in the progression of breast cancer, particularly in the late stage of breast cancer or aggressive subtypes, such as triple‐negative breast cancer (TNBC). In recent years, noni fruit ( Morinda citrifolia L.) has gained popularity as a health‐promoting fruit with multiple bioactivities, and its fermented juice exhibits potent antioxidant, anti‐inflammation, immunity‐enhancing, and potential anticancer effects. High performance liquid chromatography (HPLC) was used to identify the chemical constituents of noni fermented juice (NFJ). Breast cancer cells (MDA‐MB‐231 and MCF‐7) were treated with NFJ in in vitro experiment, and the in vivo antitumor effects were evaluated in a xenograft breast cancer model. Transcriptome and biochemical analysis were utilized to explore the therapeutic targets and signaling pathway by NFJ. Our findings demonstrated that NFJ showed significant antitumor effects by suppressing the cell viability, migration, invasion, and proliferation and inducing the apoptosis in breast cancer cells, and the antitumor effects of NFJ were further validated in vivo. The antitumor effects of NFJ were mainly mediated through the inhibition on angiogenesis via Ikkβ/NF‐κB/VEGF pathway. Our study identified NFJ as an effective and safe antitumor agent by inhibiting the angiogenesis in breast cancer, which the potential mechanism of action was the regulation of NF‐κB signaling.