Niacin alleviates TRAIL-mediated colon cancer cell death via autophagy flux activation

被引:33
作者
Kim, Sung-Wook [1 ]
Lee, Ju-Hee [1 ]
Moon, Ji-Hong [1 ]
Nazim, Uddin M. D. [1 ]
Lee, You-Jin [1 ]
Seol, Jae-Won [1 ]
Hur, Jin [1 ]
Eo, Seong-Kug [1 ]
Lee, John-Hwa [1 ]
Park, Sang-Youel [1 ]
机构
[1] Chonbuk Natl Univ, Biosafety Res Inst, Dept Biochem, Coll Vet Med, Jeonju 561756, Jeonbuk, South Korea
基金
新加坡国家研究基金会;
关键词
niacin; autophagy; TRAIL; death receptor; mitochondrial membrane potential; APOPTOSIS-INDUCING LIGAND; DEFECTIVE APOPTOSIS; PROSTATE-CANCER; NEURONAL CELLS; SURVIVAL; RECEPTORS; PROTEIN; NECROSIS; MITOCHONDRIA; APO2L/TRAIL;
D O I
10.18632/oncotarget.5374
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Niacin, also known as vitamin B3 or nicotinamide is a water-soluble vitamin that is present in black beans and rice among other foods. Niacin is well known as an inhibitor of metastasis in human breast carcinoma cells but the effect of niacin treatment on TRAIL-mediated apoptosis is unknown. Here, we show that niacin plays an important role in the regulation of autophagic flux and protects tumor cells against TRAIL-mediated apoptosis. Our results indicated that niacin activated autophagic flux in human colon cancer cells and the autophagic flux activation protected tumor cells from TRAIL-induced dysfunction of mitochondrial membrane potential and tumor cell death. We also demonstrated that ATG5 siRNA and autophagy inhibitor blocked the niacin-mediated inhibition of TRAIL-induced apoptosis. Taken together, our study is the first report demonstrating that niacin inhibits TRAIL-induced apoptosis through activation of autophagic flux in human colon cancer cells. And our results also suggest that autophagy inhibitors including genetic and pharmacological tools may be a successful therapeutics during anticancer therapy using TRAIL.
引用
收藏
页码:4356 / 4368
页数:13
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