ArticleCancer medicine2013
Thiocoraline alters neuroendocrine phenotype and activates the Notch pathway in MTC-TT cell line.
Article in Cancer medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- The role of MAPK, notch and Wnt signaling pathways in papillary thyroid cancer: Evidence from a systematic review and meta-analyzing microarray datasets employing bioinformatics knowledge and literature.Biochemistry and biophysics reports · 2024Article
- Natural Cyclopeptides as Anticancer Agents in the Last 20 Years.International journal of molecular sciences · 2021Review
- Notch Signaling in Thyroid Cancer.Advances in experimental medicine and biology · 2021Review
- Thiocoraline mediates drug resistance in MCF-7 cells via PI3K/Akt/BCRP signaling pathway.Cytotechnology · 2019Article
- Histone deacetylase inhibitor thailandepsin-A activates Notch signaling and suppresses neuroendocrine cancer cell growthOncotarget · 2017Article
- Antineoplastic effects of histone deacetylase inhibitors in neuroendocrine cancer cells are mediated through transcriptional regulation of Notch1 by activator protein 1.Cancer medicine · 2017Article
- Tumor-suppressor role of Notch3 in medullary thyroid carcinoma revealed by genetic and pharmacological induction.Molecular cancer therapeutics · 2015Article
- Thiocoraline activates the Notch pathway in carcinoids and reduces tumor progression in vivo.Cancer gene therapy · 2014Article
- Biosynthetic modularity rules in the bisintercalator family of antitumor compounds.Marine drugs · 2014Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Medullary thyroid cancer (MTC) is an aggressive neuroendocrine tumor (NET). Previous research has shown that activation of Notch signaling has a tumor suppressor role in NETs. The potential therapeutic effect of thiocoraline on the activation of the Notch pathway in an MTC cell line (TT) was investigated. Thiocoraline was isolated from a marine bacterium Verrucosispora sp. MTT assay (3-[4, 5-dimethylthiazole-2-yl]-2, 5-diphenyltetrazolium bromide) was used to determine the IC50 value and to measure cell proliferation. Western blot revealed the expression of Notch isoforms, NET, and cell cycle markers. Cell cycle progression was validated by flow cytometry. The mRNA expression of Notch isoforms and downstream targets were measured using real-time PCR. The IC50 value for thiocoraline treatment in TT cells was determined to be 7.6 nmol/L. Thiocoraline treatment decreased cell proliferation in a dose- and time-dependent manner. The mechanism of growth inhibition was found to be cell cycle arrest in G1 phase. Thiocoraline activated the Notch pathway as demonstrated by the dose-dependent increase in mRNA and protein expression of Notch isoforms. Furthermore, treatment with thiocoraline resulted in changes in the expression of downstream targets of the Notch pathway (HES1, HES2, HES6, HEY1, and HEY2) and reduced expression of NET markers, CgA, and ASCL1. Thiocoraline is a potent Notch pathway activator and an inhibitor of MTC-TT cell proliferation at low nanomolar concentrations. These results provide exciting evidence for the use of thiocoraline as a potential treatment for intractable MTC.
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