Korean J Intern Med.  2014 Jul;29(4):474-481.

The effect of 5-aminoimidazole-4-carboxamide-ribonucleoside was mediated by p38 mitogen activated protein kinase signaling pathway in FRO thyroid cancer cells

Affiliations
  • 1Division of Endocrinology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. tykim@amc.seoul.kr
  • 2Asan Institute for Life Science, Seoul, Korea.

Abstract

BACKGROUND/AIMS
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-alpha1 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.

Keyword

Thyroid neoplasms; AMP-activated protein kinases; p38 mitogen-activated protein kinases; AICA ribonucleotide

MeSH Terms

AMP-Activated Protein Kinases/genetics/metabolism
Aminoimidazole Carboxamide/*analogs & derivatives/pharmacology
Antineoplastic Agents/*pharmacology
Caspase 3/metabolism
Cell Line, Tumor
Cell Proliferation/drug effects
Cell Survival/drug effects
Cyclin-Dependent Kinase Inhibitor p21/metabolism
Dose-Response Relationship, Drug
Enzyme Activation
Enzyme Activators/pharmacology
Humans
Mutation
Protein Kinase Inhibitors/pharmacology
Proto-Oncogene Proteins B-raf/genetics
RNA Interference
Ribonucleotides/*pharmacology
Signal Transduction/*drug effects
Thyroid Neoplasms/*enzymology/genetics/pathology
Time Factors
Transfection
p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
AMP-Activated Protein Kinases
Aminoimidazole Carboxamide
Antineoplastic Agents
Caspase 3
Cyclin-Dependent Kinase Inhibitor p21
Enzyme Activators
Protein Kinase Inhibitors
Proto-Oncogene Proteins B-raf
Ribonucleotides
p38 Mitogen-Activated Protein Kinases
Full Text Links
  • KJIM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr