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Updated: Jan 7, 2026

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
Published on: April 17, 2013
SOX2/SOX17 Molecular Switching by Polyphenols to Promote Thyroid Differentiation in 2D and 3D Models of Anaplastic
Fabiola Vaglica1, Mattia Biondo2, Giuseppe Siragusa2
1Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro" (Promise), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, PA, Italy.
Abstract:
Deep alterations in tumor cell gene profiles resulting in the loss of their specific functions are frequently the cause of resistance to traditional cancer treatments. Therefore, reprogramming the expression pattern of cancer cells toward a differentiated phenotype represents a promising therapeutic strategy. In this study, we investigated whether resveratrol (RSV) and its natural analogs-3,4',5-trimethoxystilbene (3-MET-OX) and isorhapontigenin (ISOR-H-PG)-can modulate the SOX2/SOX17 balance and promote re-differentiation in anaplastic thyroid cancer (ATC) cells. Two human ATC cell lines (SW1736 and 8505c) and non-tumoral thyroid cells (Nthy-ori 3-1) were cultured in two-dimensional (2D) or three-dimensional (3D) systems and treated with polyphenols at sub-cytotoxic doses. In 2D cultures, cell viability and cell cycle analyses confirmed a cytostatic effect characterized by G1 arrest. In 3D cultures, polyphenol treatment caused morphological disruption of ATC spheroids and significantly modulated the gene expression profile. RSV and 3-MET-OX reduced stemness markers (SOX2, NANOG), increased the thyroid lineage transcription factor (SOX17), and enhanced differentiation genes (TTF-1, TPO, NIS). Overall, these results support our hypothesis that modulation of the SOX2/SOX17 ratio by polyphenols provides a mechanistic basis for re-differentiation, thereby improving therapeutic responsiveness in ATC.
Insights
Resveratrol (RSV) and its analogs re-differentiate anaplastic thyroid cancer (ATC) cells by modulating SOX2/SOX17 balance. This polyphenol treatment offers a promising strategy to improve therapeutic responsiveness in ATC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Cancer treatment resistance often stems from altered tumor cell gene profiles.
- Reprogramming cancer cells toward a differentiated phenotype is a promising therapeutic strategy.
Purpose of the Study:
- To investigate if resveratrol (RSV) and its analogs (3-MET-OX, ISOR-H-PG) can modulate the SOX2/SOX17 balance and promote re-differentiation in anaplastic thyroid cancer (ATC) cells.
- To assess the effects of these polyphenols on gene expression and differentiation markers in ATC cells.
Main Methods:
- Human ATC cell lines (SW1736, 8505c) and non-tumoral thyroid cells (Nthy-ori 3-1) were cultured in 2D and 3D systems.
- Cells were treated with sub-cytotoxic doses of RSV, 3-MET-OX, and ISOR-H-PG.
- Analyses included cell viability, cell cycle, spheroid morphology, and gene expression profiling.
Main Results:
- Polyphenol treatment induced G1 arrest in 2D cultures, indicating a cytostatic effect.
- In 3D cultures, polyphenols disrupted ATC spheroids and modulated gene expression.
- RSV and 3-MET-OX reduced stemness markers (SOX2, NANOG) and increased differentiation markers (SOX17, TTF-1, TPO, NIS).
Conclusions:
- Modulation of the SOX2/SOX17 ratio by RSV and its analogs provides a mechanistic basis for ATC cell re-differentiation.
- This polyphenol-induced re-differentiation strategy holds potential for improving therapeutic responsiveness in anaplastic thyroid cancer.
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