Selective Antitumor Activity of Datelliptium toward Medullary Thyroid Carcinoma by Downregulating RET Transcriptional...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Medullary thyroid carcinoma (MTC) is an aggressive thyroid cancer characterized by high metastatic rates.
• Mutations in the REarranged during Transfection (RET) proto-oncogene drive both sporadic and hereditary MTC.
• Datelliptium was previously identified as a RET transcription inhibitor that stabilizes RET G-quadruplex structures.

Purpose of the Study:

• To investigate the effect of datelliptium on suppressing epithelial-to-mesenchymal transition (EMT) in MTC cells.
• To evaluate datelliptium's impact on MTC cell migration and cancer stem cell (CSC) formation.
• To assess datelliptium's efficacy in inhibiting MTC tumor growth in vivo.

Main Methods:

• Datelliptium's effect on mesenchymal markers (N-cadherin, vimentin, slug, snail, claudin-1) was assessed.
• Wound healing assays were used to measure TT cell migration.
• Spheroid formation assays evaluated cancer stem cell properties.
• MTC xenograft models were utilized to determine in vivo efficacy and toxicity.

Main Results:

• Datelliptium significantly downregulated mesenchymal markers, indicating suppression of EMT.
• A dose-dependent decrease in TT cell migration was observed.
• Datelliptium reduced spheroid size, suggesting inhibition of CSC self-renewal.
• Approximately 75% inhibition of MTC xenograft growth was achieved with minimal toxicity.

Conclusions:

• Datelliptium effectively reduces EMT, migration, and CSC self-renewal in MTC cells.
• Datelliptium demonstrates significant antitumor activity against MTC by preventing invasive and metastatic behaviors.
• Datelliptium presents a promising therapeutic agent for medullary thyroid carcinoma treatment.