Resveratrol induces apoptosis in thyroid cancer cell lines via a MAPK- and p53-dependent mechanism

Ai Shih, Faith B. Davis, Hung Y. Lin, Paul J. Davis

研究成果: 雜誌貢獻文章同行評審

180 引文 斯高帕斯(Scopus)

摘要

Two papillary thyroid carcinoma (PTC) and two follicular thyroid carcinoma (FTC) cell lines treated with resveratrol (RV), 1-10 μM, showed activation and nuclear translocation of MAPK (extracellular signal-regulated kinase 1/2). Cellular abundance of the oncogene suppressor protein p53, serine phosphorylation of p53, and abundance of c-fos, c-jun, and p21 mRNAs were also increased by RV. Inhibition of the MAPK pathway by either H-ras antisense transfection or PD 98059, an MAPK kinase inhibitor, blocked these RV-induced effects. Addition of pifithrin-α, a specific inhibitor of p53, or transfection of p53 antisense oligonucleotides caused decreased RV-induced p53 and p21 expression in PTC and FTC cells. Studies of nucleosome levels estimated by ELISA and of DNA fragmentation showed that RV induced apoptosis in both papillary and follicular thyroid cancer cell lines; these effects were inhibited by pifithrin-α and by p53 antisense oligonucleotide transfection. PD 98059 and H-ras antisense transfection also blocked induction of apoptosis by RV. Thus, RV acts via a Ras-MAPK kinase-MAPK signal transduction pathway to increase p53 expression, serine phosphorylation of p53, and p53-dependent apoptosis in PTC and FTC cell lines.
原文英語
頁(從 - 到)1223-1232
頁數10
期刊Journal of Clinical Endocrinology and Metabolism
87
發行號3
DOIs
出版狀態已發佈 - 2002
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 內分泌學、糖尿病和代謝

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