Magnolol-Induced Apoptosis in HCT-116 Colon Cancer Cells Is Associated with the AMP-Activated Protein Kinase Signaling Pathway
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概要
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Colon cancer is the third most common malignancy around the world. Surgery, chemotherapy, and radiotherapy are generally used to treat colon cancer, but no effective therapy for advanced colon carcinoma is available. Therefore, there is a need to identify other therapeutic agents against this disease. Magnolol, a hydroxylated biphenyl compound present in Magnolia officinalis, exerts anticancer potential and low toxicity. Emerging evidence has suggested that activation of AMP-activated protein kinase (AMPK), a potential cancer therapeutic target is involved in apoptosis in colon cancer cells. However, the effects of magnolol on human colon cancer through activation of AMPK remain unexplored. In this study, we explored whether magnolol exerts an antiproliferative effect, and induces apoptosis in HCT-116 human colon cancer cells. Magnolol displayed several apoptotic features, including propidium iodide labeling, DNA fragmentation, and caspase-3 and poly(ADP-ribose) polymerase cleavages. We showed that magnolol induced the phosphorylation of AMPK in dose- and time-dependent manners. The selective AMPK inhibitor compound C abrogated the effect of magnolol on AMPK activation, suppression of proliferation, and caspase-3 cleavage. Magnolol downregulated expression of the antiapoptotic protein Bcl2, upregulated expression of pro-apoptotic protein p53 and Bax, and caused the release of mitochondrial cytochrome c. Magnolol-induced p53 and Bcl2 expression was abolished in the presence of compound C. Magnolol inhibited migration and invasion of HCT-116 cells through AMPK activation. These findings demonstrate that AMPK mediates the anticancer effects of magnolol through apoptosis in HCT-116 cells.
- 公益社団法人 日本薬学会の論文
著者
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Kim Ji
Department Of Anesthesiology And Pain Medicine Gachon Medical School Gil Medical Center
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Sul Ji
Department of Surgery, Chungnam National University Hospital
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Song In
Department Of Anatomy And Aging-associated Vascular Disease Research Center College Of Medicine Yeun
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Lee Jin
Department Of Biology Inha University
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Park Jun
Department Of Computer Science Hongik University
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Lee Myung
Surgical Oncology Research Lab, Regional Cancer Institute, Chungnam National University Hospital
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Cha Eun
Surgical Oncology Research Lab, Regional Cancer Institute, Chungnam National University Hospital
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Lee Jin
Department of Surgery, Chungnam National University Hospital
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Sul Ji
Department of Surgery and Research Institute for Medicinal Sciences, Chungnam National University School of Medicine
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Park Jun
Department of Applied Physics, Kyung Hee University, Yongin 446-701, Korea
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Kim Ji
Department of Advanced Materials Engineering, Sangju National University, Kyeongbuk 742-711, Korea
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Song In
Department of Advanced Material Engineering, Daejeon University, Daejeon 300-716, Republic of Korea
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LEE Jin
Department of Biochemistry, College of Medicine, Inje University
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Kim Ji
Department of Surgery, Chungnam National University Hospital
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