title: Niacin alleviates TRAIL-mediated colon cancer cell death via autophagy flux activation.
abstract: 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.
authors.affiliation: Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: Sung-Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Moon
authors.affiliation: Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: Uddin M D
authors.initials: UM
authors.lastname: Nazim
authors.affiliation: Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Seol
authors.affiliation: Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Hur
authors.affiliation: Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: Seong-Kug
authors.initials: SK
authors.lastname: Eo
authors.affiliation: Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: John-Hwa
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D009525:Niacin / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014665:Vasodilator Agents; D009525:Niacin
keywords: TRAIL; autophagy; death receptor; mitochondrial membrane potential; niacin