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

Abstract

Background/Aims5'-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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.

Induction of Apoptosis in Human Papillary-Thyroid-Carcinoma BCPAP Cells by Diallyl Trisulfide through Activation of the MAPK Signaling Pathway

“…Sorafenib, an oral multikinase inhibitor, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of 131 I-refractory and metastatic thyroid cancer. Though sorafenib is currently considered a first-line therapy for 131 I-refractory metastatic PTC, 19 the diseases of a proportion of patients are still in progress even after the treatment. Therefore, it is urgent to develop promising drugs or novel strategies to improve the therapeutic efficiency.…”

“…In mammalian cells, this superfamily consists of three main members: extracellular-regulated kinase (ERK), c-Jun Nterminal kinase (JNK), and p38. 19 The MAPK signaling pathway participates in various cell behaviors, including cell proliferation, differentiation, and apoptosis. 20 The activation of JNK−p38 is a kind of apoptotic signal, whereas the activation of ERK is generally a survival signal.…”

“…Mitogen-activated protein kinases (MAPKs) are serine–threonine kinases. In mammalian cells, this superfamily consists of three main members: extracellular-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 . The MAPK signaling pathway participates in various cell behaviors, including cell proliferation, differentiation, and apoptosis .…”