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Inhibition of malignant thyroid carcinoma cell proliferation by Ras and galectin-3 inhibitors

A Menachem1, O Bodner1, J Pastor1

  • 1Department of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University , Tel Aviv, Israel.

Cell Death Discovery
|August 24, 2016
PubMed

Insights

This study introduces a novel combination therapy using S-trans, transfarnesylthiosalicylic acid (FTS) and modified citrus pectin (MCP) to combat aggressive anaplastic thyroid carcinoma. The treatment effectively inhibited tumor growth by targeting K-Ras and Galectin-3 pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Anaplastic thyroid carcinoma (ATC) is a highly aggressive and often fatal malignancy.
  • Galectin-3 (Gal-3) is a key marker in thyroid carcinomas and a scaffold for K-Ras.
  • Ras inhibitors like FTS and Gal-3 inhibitors like MCP offer potential therapeutic avenues.

Purpose of the Study:

  • To develop and evaluate a novel drug combination therapy for aggressive anaplastic thyroid carcinoma.
  • To investigate the combined effects of FTS and MCP on ATC cell proliferation and tumor growth.
  • To identify key molecular targets and pathways modulated by the FTS and MCP combination.

Main Methods:

  • In vitro studies using anaplastic thyroid carcinoma cell lines treated with FTS and MCP.
  • In vivo studies using nude mouse xenograft models of anaplastic thyroid carcinoma.
  • Immunoblot analysis to assess protein expression levels (Pan-Ras, K-Ras, Ras-GTP, p-ERK, p53, Gal-3, p21).

Main Results:

  • Combined FTS and MCP treatment significantly inhibited ATC cell proliferation in vitro by inducing cell cycle arrest and apoptosis.
  • Western blot analysis showed decreased levels of Pan-Ras, K-Ras, Ras-GTP, p-ERK, p53, and Gal-3, with increased p21 expression.
  • In vivo, FTS and MCP combination therapy suppressed tumor growth in nude mice, with reduced levels of Gal-3, K-Ras-GTP, and p-ERK.

Conclusions:

  • K-Ras and Galectin-3 are identified as crucial molecular targets in anaplastic thyroid tumors.
  • The combination of FTS and MCP represents a promising novel therapeutic strategy for aggressive anaplastic thyroid carcinoma.
  • This approach warrants further investigation for clinical application in treating this deadly cancer.

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