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Selective repression of RET proto-oncogene in medullary thyroid carcinoma by a natural alkaloid berberine

Vishnu Muthuraj Kumarasamy1, Yoon-Joo Shin2, John White3

  • 1College of Pharmacy, University of Arizona, Tucson, Arizona, 85721. vishnuk@email.arizona.edu.

BMC Cancer
|August 27, 2015
PubMed
Abstract

Insights

Berberine stabilizes G-quadruplex structures to suppress RET proto-oncogene transcription, offering a new therapeutic strategy for medullary thyroid carcinoma (MTC). This natural compound effectively inhibits MTC cell proliferation and induces apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Gain-of-function mutations in the RET proto-oncogene are linked to medullary thyroid carcinoma (MTC).
  • The RET receptor tyrosine kinase is a key target for MTC therapy.
  • Targeting RET transcription offers a potential therapeutic strategy for advanced MTC.

Purpose of the Study:

  • To investigate berberine as a therapeutic agent for MTC.
  • To explore the mechanism of berberine in suppressing RET proto-oncogene transcription.
  • To evaluate the effect of berberine on MTC cell proliferation and survival.

Main Methods:

  • Utilized medullary thyroid carcinoma (MTC) TT cell line to assess berberine's effects on RET expression.
  • Employed papillary thyroid carcinoma TPC1 cell line to confirm berberine's specificity.
  • Analyzed downstream signaling pathways, cell cycle regulation, and apoptosis.

Main Results:

  • Berberine suppressed RET expression by over 90% in MTC TT cells at 2.5 μg/ml.
  • Berberine inhibited cell proliferation, induced cell cycle arrest, and activated apoptosis in TT cells.
  • Berberine's analogue, canadine, showed no significant effect, highlighting berberine's specific interaction with the RET G-quadruplex.

Conclusions:

  • Stabilization of the RET promoter G-quadruplex structure is critical for berberine's transcriptional repression.
  • Berberine represents a promising therapeutic strategy for MTC by targeting RET transcription.
  • G-quadruplex stabilization offers a novel approach for cancer therapy.

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