title: Inhibition of malignant thyroid carcinoma cell proliferation by Ras and galectin-3 inhibitors.
abstract: Anaplastic Thyroid carcinoma is an extremely aggressive solid tumor that resists most treatments and is almost always fatal. Galectin-3 (Gal-3) is an important marker for thyroid carcinomas and a scaffold of the K-Ras protein. S-trans, transfarnesylthiosalicylic acid (FTS; Salirasib) is a Ras inhibitor that inhibits the active forms of Ras proteins. Modified citrus pectin (MCP) is a water-soluble citrus-fruit-derived polysaccharide fiber that specifically inhibits Gal-3. The aim of this study was to develop a novel drug combination designed to treat aggressive anaplastic thyroid carcinoma. Combined treatment with FTS and MCP inhibited anaplastic thyroid cells proliferation in vitro by inducing cell cycle arrest and increasing apoptosis rate. Immunoblot analysis revealed a significant decrease in Pan-Ras, K-Ras, Ras-GTP, p-ERK, p53, and Gal-3 expression levels and significant increase in p21 expression levels. In nude mice, treatment with FTS and MCP inhibited tumor growth. Levels of Gal-3, K-Ras-GTP, and p-ERK were significantly decreased. To conclude, our results suggest K-Ras and Gal-3 as potential targets in anaplastic thyroid tumors and herald a novel treatment for highly aggressive anaplastic thyroid carcinoma.
authors.affiliation: Department of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University , Tel Aviv, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Menachem
authors.affiliation: Department of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University , Tel Aviv, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Bodner
authors.affiliation: Department of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University , Tel Aviv, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Pastor
authors.affiliation: The Departments of Oncology and Pathology, School of Medicine, The Karmanos Cancer Institute, Wayne State University , Detroit, MI, USA.
authors.forename: A
authors.initials: A
authors.lastname: Raz
authors.affiliation: Department of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University , Tel Aviv, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Kloog