In vitro and in vivo anti-tumor efficacy of krill oil against bladder cancer: Involvement of tumor-associated angiogenic vasculature
- Authors
- Kim, Hoon; Roh, Youngjin; Park, Sang Yong; Lee, Chungil; Lim, Sujin; Cho, Seongbin; Lee, Hyang-Yeol; Hong, Soon Auck; Lee, Tae Jin; Myung, Soon Chul; Yun, Seok-Joong; Choi, Yung Hyun; Kim, Wun-Jae; Moon, Sung-Kwon
- Issue Date
- Jun-2022
- Publisher
- Elsevier Ltd
- Keywords
- Acute toxicity test; Aortic ring; Krill oil; Tumor-associated angiogenic vasculature; Xenograft mice
- Citation
- Food Research International, v.156
- Journal Title
- Food Research International
- Volume
- 156
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/57723
- DOI
- 10.1016/j.foodres.2022.111144
- ISSN
- 0963-9969
1873-7145
- Abstract
- Krill oil (KO) obtained from Euphausia superba is nutrient-rich and has a positive effect on human health. Here, we explored the efficacy of KO in inhibiting tumor progression and tumor vascularization. KO (100–300 μg/mL) repressed the proliferation of bladder tumor cell lines MBT-2 and T24. Treatment of cells with KO raised cell-cycle arrest at G0/G1-phase via modulation of positive regulators and negative regulators in bladder cancer cells. KO treatment regulated phosphorylation of proteins involved in PI3K/AKT and MAPK signaling pathways, including ERK, JNK, and p38 MAPK. Additionally, KO hampered the invasion and migration of both cell lines via reduction of MMP-9 expression levels by disrupting transcriptional binding of Sp-1, AP-1, and NF-κB motifs. Moreover, in animal studies, KO (150–300 mg/kg) significantly decreased tumor growth in xenograft mice bearing T24 tumor cells. No significant toxic effects were observed in acute toxicity tests, including biological analysis and H&E staining. The reduced level of CD31 expression in KO-treated tumor tissues prompted us to investigate the effect of KO on tumor angiogenesis. KO (5–40 μg/mL) treatment impeded VEGF-induced capillary tube formation and proliferation by inhibiting VEGFR2-modulated eNOS/AKT/ERK1/2 signaling axis in HUVECs. Treatment of HUVECs with KO inhibited VEGF-stimulated migration and invasion by reducing MMP-2 expression level. VEGF-driven sprouting capacity of neo-microvessels was suppressed in the presence of KO (20–40 μg/mL), as determined via an ex vivo aortic ring assay. Our results indicated that KO can regulate both tumor growth and tumor-associated angiogenesis via a novel mechanism. Thus, KO may be a promising antitumor candidate, potentially useful to prevent or treat bladder cancer. © 2022 Elsevier Ltd
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