Title:Inactivation of PDH can Reduce Anaplastic Thyroid Cancer Cells’ Sensitivity to Artemisinin
Volume: 22
Issue: 9
Author(s): Yitian Li*
Affiliation:
- Research Department of Jining Medical University, Jining, Shandong, China
Keywords:
Anaplastic thyroid cancer, artemisinin, tolerance, oxidative phosphorylation, HIF1α, PDK1.
Abstract:
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.