ArticleBMC cancer2015
Selective repression of RET proto-oncogene in medullary thyroid carcinoma by a natural alkaloid berberine.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Loss of WT1 Drives Adaptive Plasticity in CCDC6-RET Selpercatinib-Resistant Papillary Thyroid Cancer.Current issues in molecular biology · 2026Article
- Canadine protects against doxorubicin-induced cardiac and brain injury by inhibiting Oxidative stress.BMC pharmacology & toxicology · 2026Article
- A novel role for nonactin: interfering with G-quadruplex in RET-driven medullary thyroid cancer.BMC cancer · 2024Article
- Canadine inhibits epithelial mesenchymal transformation of HPV-negative cervical cancer.Tissue barriers · 2024Article
- Promising Role of Alkaloids in the Prevention and Treatment of Thyroid Cancer and Autoimmune Thyroid Disease: A Comprehensive Review of the Current Evidence.International journal of molecular sciences · 2024Review
- Berberine: An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways.Molecules (Basel, Switzerland) · 2022Review
- Berberine as a Potential Anticancer Agent: A Comprehensive Review.Molecules (Basel, Switzerland) · 2021Review
- G-quadruplex DNA: a novel target for drug design.Cellular and molecular life sciences : CMLS · 2021Review
- Article
- Bulged and Canonical G-Quadruplex Conformations Determine NDPK Binding Specificity.Molecules (Basel, Switzerland) · 2019Article
- Identification and characterization of G-quadruplex formation within the EP0 promoter of pseudorabies virus.Scientific reports · 2018Article
- Demonstration of a potent RET transcriptional inhibitor for the treatment of medullary thyroid carcinoma based on an ellipticine derivative.International journal of oncology · 2017Article
- Review
- Ligand binding to telomeric G-quadruplex DNA investigated by funnel-metadynamics simulations.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Article
- The Management of Medullary Thyroid Carcinoma in the Era of Targeted Therapy.European endocrinology · 2016Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe gain-of-function mutation of the RET proto-oncogene, which encodes a receptor tyrosine kinase, is strongly associated with the development of several medullary thyroid carcinomas (MTCs). Thus, the RET protein has been explored as an excellent target for progressive and advanced MTC. In this study we have demonstrated a therapeutic strategy for MTC by suppressing the transcription of RET proto-oncogene though the stabilization of G-quadruplex structure formed on the promoter region of this gene using a natural product berberine.
methodsMedullary thyroid carcinoma (MTC) TT cell line has been used to evaluate the effects of berberine on RET expression and its downstream signaling pathways. The specificity of berberine was demonstrated by using the papillary thyroid carcinoma TPC1 cell line, which lacks the G-quadruplex forming sequence on the RET promoter region due to chromosomal rearrangement.
resultsBerberine suppressed the RET expression by more than 90 % in MTC TT cells at a concentration of 2.5 μg/ml with minimal effect on the TPC1 cells. Canadine, which is a structural analogue of berberine, showed little interaction with RET G-quadruplex and also had no effect on RET expression in MTC TT cells. The down-regulation of RET with berberine further inhibited the cell proliferation through cell cycle arrest and activation of apoptosis in TT cells, which was confirmed by a 2-fold increase in the caspase-3 activity and the down-regulation of cell-cycle regulatory proteins.
conclusionOur data strongly suggest that the G-quadruplex forming region and the stabilization of this structure play a critical role in mediating the repressive effect of berberine on RET transcription.
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