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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Inactivation of PDH can Reduce Anaplastic Thyroid Cancer Cells’ Sensitivity to Artemisinin

Author(s): Yitian Li*

Volume 22, Issue 9, 2022

Published on: 03 January, 2022

Page: [1753 - 1760] Pages: 8

DOI: 10.2174/1871520621666210910100803

Price: $65

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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.

Keywords: Anaplastic thyroid cancer, artemisinin, tolerance, oxidative phosphorylation, HIF1α, PDK1.

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