title: The effect of 5-aminoimidazole-4-carboxamide-ribonucleoside was mediated by p38 mitogen activated protein kinase signaling pathway in FRO thyroid cancer cells.
abstract: OBJECTIVE
  5'-Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a cellular energy sensor that monitors intracellular AMP/adenosine triphosphate (ATP) ratios and is a key regulator of the proliferation and survival of diverse malignant cell types. In the present study, we investigated the effect of activating AMPK by 5-aminoimidazole-4-carboxamide-ribonucleotide (AICAR) in thyroid cancer cells.
  
  
  METHODS
  We used FRO thyroid cancer cells harboring the BRAF(V600E) mutation to examine the effect of AICAR on cell proliferation and cell survival. We also evaluated the involvement of mitogen-activated protein kinase (MAPK) pathways in this effect.
  
  
  RESULTS
  We found that AICAR treatment promoted AMPK activation and suppressed cell proliferation and survival by inducing p21 accumulation and activating caspase-3. AICAR significantly induced activation of p38 MAPK, and pretreatment with SB203580, a specific inhibitor of the p38 MAPK pathway, partially but significantly rescued cell survival. Furthermore, small interfering RNA targeting AMPK-α1 abolished AICAR-induced activation of p38 MAPK, p21 accumulation, and activation of caspase-3.
  
  
  CONCLUSIONS
  Our findings demonstrate that AMPK activation using AICAR inhibited cell proliferation and survival by activating p38 MAPK and proapoptotic molecules in FRO thyroid cancer cells. These results suggest that the AMPK and p38 MAPK signaling pathways may be useful therapeutic targets to treat thyroid cancer.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Won Gu
authors.initials: WG
authors.lastname: Kim
authors.affiliation: Asan Institute for Life Science, Seoul, Korea.
authors.forename: Hyun-Jeung
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shong
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Won Bae
authors.initials: WB
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D006801:Humans; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D034622:RNA Interference; D012265:Ribonucleotides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D020536:Enzyme Activators; D047428:Protein Kinase Inhibitors; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; C031143:AICA ribonucleotide
keywords: AICA ribonucleotide; AMP-activated protein kinases; Thyroid neoplasms; p38 mitogen-activated protein kinases