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KMID : 0338420140290040474
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The Korean Journal of Internal Medicine
2014 Volume.29 No. 4 p.474 ~ p.481
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The effect of 5-aminoimidazole-4-carboxamideribonucleoside was mediated by p38 mitogen activated protein kinase signaling pathway in FRO thyroid cancer cells
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Kim Won-Gu
Choi Hyun-Jeung
Kim Tae-Yong
Shong Young-Kee
Kim Won-Bae
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Abstract
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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 BRAFV600E 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.
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KEYWORD
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Thyroid neoplasms, AMP-activated protein kinases, p38 mitogen-activated protein kinases, AICA ribonucleotide
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