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Updated: Jul 5, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Evaluation of the Therapeutic Effects of Harmine on Anaplastic Thyroid Cancer Cells
Enke Baldini1, Silvia Cardarelli1, Antonio Francesco Campese2
1Department of Surgery, "Sapienza" University of Rome, 00161 Rome, Italy.
Abstract:
Anaplastic thyroid carcinoma (ATC) is an extremely difficult disease to tackle, with an overall patient survival of only a few months. The currently used therapeutic drugs, such as kinase inhibitors or immune checkpoint inhibitors, can prolong patient survival but fail to eradicate the tumor. In addition, the onset of drug resistance and adverse side-effects over time drastically reduce the chances of treatment. We recently showed that Twist1, a transcription factor involved in the epithelial mesenchymal transition (EMT), was strongly upregulated in ATC, and we wondered whether it might represent a therapeutic target in ATC patients. To investigate this hypothesis, the effects of harmine, a β-carboline alkaloid shown to induce degradation of the Twist1 protein and to possess antitumoral activity in different cancer types, were evaluated on two ATC-derived cell lines, BHT-101 and CAL-62. The results obtained demonstrated that, in both cell lines, harmine reduced the level of Twist1 protein and reverted the EMT, as suggested by the augmentation of E-cadherin and decrease in fibronectin expression. The drug also inhibited cell proliferation and migration in a dose-dependent manner and significantly reduced the anchorage-independent growth of both ATC cell lines. Harmine was also capable of inducing apoptosis in BHT-101 cells, but not in CAL-62 ones. Finally, the activation of PI3K/Akt signaling, but not that of the MAPK, was drastically reduced in treated cells. Overall, these in vitro data suggest that harmine could represent a new therapeutic option for ATC treatment.
Insights
Harmine effectively targets Twist1 in anaplastic thyroid carcinoma (ATC), inhibiting cancer cell growth and migration. This study suggests harmine as a potential new therapeutic strategy for difficult-to-treat ATC.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Anaplastic thyroid carcinoma (ATC) has a poor prognosis with limited treatment options.
- Current therapies like kinase and immune checkpoint inhibitors offer survival benefits but do not eradicate tumors and face resistance.
- Twist1, a transcription factor driving epithelial-mesenchymal transition (EMT), is upregulated in ATC and presents a potential therapeutic target.
Purpose of the Study:
- To investigate the therapeutic potential of harmine against anaplastic thyroid carcinoma.
- To evaluate harmine's effects on Twist1 protein levels and EMT markers in ATC cell lines.
- To assess harmine's impact on cell proliferation, migration, anchorage-independent growth, apoptosis, and signaling pathways.
Main Methods:
- Treatment of ATC cell lines (BHT-101 and CAL-62) with varying doses of harmine.
- Assessment of Twist1 protein levels, EMT markers (E-cadherin, fibronectin), cell proliferation, migration, and apoptosis.
- Analysis of PI3K/Akt and MAPK signaling pathway activation.
Main Results:
- Harmine significantly reduced Twist1 protein levels and reverted EMT in both ATC cell lines.
- The drug inhibited cell proliferation, migration, and anchorage-independent growth in a dose-dependent manner.
- Harmine induced apoptosis in BHT-101 cells and suppressed PI3K/Akt signaling.
Conclusions:
- Harmine demonstrates significant anti-cancer activity against ATC cells in vitro.
- The drug's ability to target Twist1 and inhibit EMT suggests its potential as a novel therapeutic agent for ATC.
- Further research into harmine's efficacy and safety is warranted for ATC treatment.
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