Inactivation of PDH can Reduce Anaplastic Thyroid Cancer Cells' Sensitivity to Artemisinin
1Research Department of Jining Medical University, Jining, Shandong, China.
Background:
Anaplastic Thyroid Cancer (ATC) is a rare subtype of thyroid tumors with a high mortality rate. Targeted therapies against ATC are ineffective and mostly transient. Artemisinin has shown excellent anti-tumor activity in several cancers, but its effects on ATC are still unknown.
Objective:
To evaluate the effects of artemisinin on ATC cells and assess the mechanism underlying drug resistance.
Methods:
The viability and proliferation rates of the artemisinin-treated CAL-62 and BHT-101 cells were analyzed by MTT and EdU incorporation assays. The protein expression levels were determined by Tandem Mass Tag (TMT) labeling quantitative proteomics and western blotting.
Results:
Artemisinin treatment significantly decreased the expression levels of COX2 and COX7A2 and increased that of COX14, YEM1l1, ALAS1, and OAT after 48h. In addition, FTL was upregulated in the CAL-62 cells and downregulated in BHT-101 cells. The CAL-62 cells showed transient and reversible resistance to artemisinin, which was correlated to time-dependent changes in HIF1α, PDK1, and PDHA levels.
Conclusion:
Artemisinin targets the mitochondrial respiratory chain proteins in ATC cells. CAL-62 cells show transient resistance to artemisinin via PDH downregulation, indicating that PDH activation may enhance the cytotoxic effects of artemisinin on ATC cells.
Insights
Artemisinin shows anti-tumor effects on Anaplastic Thyroid Cancer (ATC) cells by targeting mitochondrial proteins. However, CAL-62 cells develop transient resistance, suggesting PDH activation could improve artemisinin efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Anaplastic Thyroid Cancer (ATC) is a rare, aggressive thyroid cancer with poor prognosis.
- Current targeted therapies for ATC often show limited and temporary effectiveness.
- Artemisinin, known for its anti-cancer properties, has not been studied in ATC.
Purpose of the Study:
- To investigate the anti-tumor effects of artemisinin on Anaplastic Thyroid Cancer cells.
- To elucidate the molecular mechanisms behind artemisinin resistance in ATC.
Main Methods:
- Cell viability and proliferation assessed using MTT and EdU assays.
- Protein expression analyzed via quantitative proteomics (TMT labeling) and western blotting.
- Specific cell lines used: CAL-62 and BHT-101.
Main Results:
- Artemisinin altered expression of key mitochondrial proteins, including decreased COX2/COX7A2 and increased COX14/YEM1l1/ALAS1/OAT.
- Differential regulation of FTL observed between CAL-62 and BHT-101 cell lines.
- CAL-62 cells exhibited transient resistance linked to HIF1α, PDK1, and PDHA level changes.
Conclusions:
- Artemisinin impacts mitochondrial respiratory chain proteins in ATC cells.
- Transient resistance in CAL-62 cells is associated with PDH downregulation.
- Activating pyruvate dehydrogenase (PDH) may enhance artemisinin's cytotoxic effects on ATC.
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