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AMPK/p53轴对于α-硫辛酸调节人源和鼠源结肠癌细胞的转移至关重要。

AMPK/p53 Axis Is Essential for α-Lipoic Acid-Regulated Metastasis in Human and Mouse Colon Cancer Cells.

作者信息

Park Sunmi, Choi Seung Kug, Choi Yura, Moon Hyun-Seuk

机构信息

From the *Laboratory of Metabolic Engineering, Department of Biotechnology, College of Life Sciences and Biotechnology, †Institute of Animal Molecular Biotechnology, and ‡Biomedical Research Center of Guro Hospital, Research Driven Hospital, Korea University, Seoul, South Korea.

出版信息

J Investig Med. 2015 Oct;63(7):882-5. doi: 10.1097/JIM.0000000000000233.

Abstract

α-Lipoic acid (ALA) has an anticancer property of lung, cervix, and prostate cancer cells. However, direct evidence that ALA contributes to the development of colon cancer has not been fully elucidated. In addition, no previous studies have evaluated whether ALA may regulate malignant potential, such as adhesion, invasion, and colony formation of colon cancer cells. To address the aforementioned questions, we conducted in vitro ALA signaling studies using human (HT29) and mouse (MCA38) colon cancer cell lines. We observed that cell proliferation is reduced by ALA administration in a dose-dependent manner in human and mouse colon cancer cell lines. Specifically, 0.5 to 1 mM concentration of ALA significantly decreased cell proliferation when compared with control. Similarly, we found that ALA downregulates adhesion, invasion, and colony formation. Finally, we observed that ALA activates p53 and AMPK signaling pathways in human and mouse colon cancer cells. We found for the first time that ALA suppresses cell proliferation and malignant potential via p53 and AMPK signaling pathways in human and mouse colon cancer cells. These new and early mechanistic studies provide a causal role of ALA in colon cancer, suggesting that ALA might be a useful agent in the management or chemoprevention of colon cancer.

摘要

α-硫辛酸(ALA)具有抗肺癌、宫颈癌和前列腺癌细胞的特性。然而,ALA促成结肠癌发生发展的直接证据尚未完全阐明。此外,以往尚无研究评估ALA是否可能调节结肠癌细胞的恶性潜能,如黏附、侵袭和集落形成。为解决上述问题,我们使用人源(HT29)和小鼠源(MCA38)结肠癌细胞系进行了体外ALA信号传导研究。我们观察到,在人和小鼠结肠癌细胞系中,给予ALA可使细胞增殖呈剂量依赖性降低。具体而言,与对照组相比,0.5至1 mM浓度的ALA显著降低了细胞增殖。同样,我们发现ALA下调了黏附、侵袭和集落形成。最后,我们观察到ALA激活了人和小鼠结肠癌细胞中的p53和AMPK信号通路。我们首次发现,ALA通过p53和AMPK信号通路抑制人和小鼠结肠癌细胞的增殖及恶性潜能。这些新的早期机制研究揭示了ALA在结肠癌中的因果作用,表明ALA可能是结肠癌管理或化学预防中的一种有用药物。

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