Role of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside in the Growth Regulation of Anaplastic Thyroid Cancer Cells Lines / 대한내분비학회지

ABSTRACT

BACKGROUND: Anaplastic thyroid carcinoma is one of the most aggressive human cancers with a median survival of only 6 months. Local surgical tumor debulking combined with radio-chemotherapy is generally used to treat this malady, but the low success rate has prompted the search for new therapeutic targets. We used 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) as an AMP-activated protein kinase (AMPK) activator to induce growth suppression and apoptosis in the anaplastic thyroid carcinoma cells. METHODS: We investigated the effect of AICAR on the proliferation of thyroid cancer cell lines (ARO, WRO and FRO) by performing methyl-thiazoletetrazolium bromide assay. We wanted to see the effect of AICAR on the apoptosis and cell cycle of the thyroid cancer cells, and we wanted to determine the mechanism of these changes. RESULTS: The proliferation of all thyroid cancer cell lines was significantly inhibited by administration of AICAR. FRO was the most susceptible cell line to AICAR treatment and so further studies were then performed with this cell line. The suppressive effect of AICAR on cell proliferation was related with phosphorylation of AMPK and the increased apoptosis. Also, cell cycle analysis revealed that progression to the G2-M phase was arrested (S-phase arrest) by AICAR treatment. S-phase arrest was associated with the increased protein expression of p21. CONCLUSION: In the anaplastic thyroid cancer cell lines, AICAR inhibited proliferation due to the arrest in the S-phase; this was accompanied with the increased expression of p21. Overall, AMPK activation by AICAR or any other pharmacological agent could be a tempting potential target for thyroid cancer therapy.