stilbenes and Adenocarcinoma--Follicular

Resveratrol, the naturally occurring polyphenolic compound characterized by anti-oxidative, anti-inflammatory and apoptotic properties, appears to contribute substantially to cardioprotection and cancer-prevention. In addition, resveratrol is believed to regulate several biological processes, mainly metabolism and aging, by modulating the mammalian silent information regulator 1 (SIRT1) of the sirtuin family. Resveratrol may arrest, among various tumors, cell growth in both papillary and follicular thyroid cancer by activation of the mitogen-activated protein kinase (MAPK) signal transduction pathway as well as increase of p53 and its phosphorylation. Finally, resveratrol also influences thyroid function by enhancing iodide trapping and, by increasing TSH secretion via activation of sirtuins and the phosphatidylinositol- 4-phosphate 5 kinase γ (PIP5Kγ) pathway, positively affects metabolism.

Topics: Adenocarcinoma, Follicular; Aging; Humans; Mitogen-Activated Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Resveratrol; Signal Transduction; Sirtuin 1; Stilbenes; Thyroid Gland; Thyroid Neoplasms; Thyrotropin; Tumor Suppressor Protein p53

Two papillary thyroid carcinoma (PTC) and two follicular thyroid carcinoma (FTC) cell lines treated with resveratrol (RV), 1-10 microM, 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-alpha, 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-alpha 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.

Topics: Adenocarcinoma, Follicular; Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Papillary; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Humans; Mitogen-Activated Protein Kinases; Phosphorylation; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Resveratrol; RNA, Messenger; Stilbenes; Thyroid Neoplasms; Tumor Cells, Cultured; Tumor Suppressor Protein p53