Abstract
Thyroid cancer is the most common endocrine malignancy, and its incidence has increased in the past decades. Selenium has been shown to have therapeutic effects against several tumors. However, its role in thyroid cancer and its underlying molecular mechanism remains to be explored. In the present study, we demonstrated that sodium selenite significantly decreased cell viability and induced G0/G1 cell cycle arrest and apoptosis in thyroid cancer cells in a dose-dependent manner. Transcriptomics revealed that sodium selenite induced intracellular reactive oxygen species (ROS) by promoting oxidative phosphorylation. Increased intracellular ROS levels inhibited the AKT/mTOR signaling pathway and upregulated EIF4EBP3. Intracellular ROS inhibition by N-acetylcysteine (NAC) ameliorated the cellular effects of sodium selenite. The in vitro findings were reproduced in xenograft thyroid tumor models. Our data demonstrated that sodium selenite exhibits strong anticancer effects against thyroid cancer cells, which involved ROS-mediated inhibition of the AKT/mTOR pathway. This suggests that sodium selenite may serve as a therapeutic option for advanced thyroid cancer.
Highlights
The increase in the worldwide incidence of thyroid cancer over the past decade has been one of the fastest among cancers [1]
These data showed that thyroid cancer cells were more sensitive to SS compared to human thyroid epithelial cells
We revealed that sodium selenite stimulated the accumulation of intracellular reactive oxygen species (ROS) by upregulating mitochondrial electron transport chain (mETC) components and suppressing the AKT/ mTOR pathway
Summary
The increase in the worldwide incidence of thyroid cancer over the past decade has been one of the fastest among cancers [1]. The normal progression of the cell cycle is regulated by various cyclindependent kinases (CDKs) and their partner cyclins. Continuous cell proliferation caused by uncontrolled cell division is one of the most important pathological manifestations involved in cancer progression. The continuing ROS production forces cancer cells to develop effective ROS detoxification mechanisms, and the dependence on the antioxidant system increases cancer cells’ vulnerability to oxidative stress [8]. By increasing oxidant production above the toxicity threshold, tumor cells can be killed via cell cycle arrest and apoptosis, while normal cells would be preserved. Strategies aimed at inhibiting abnormal cell proliferation by altering the redox state in tumor cells open new avenues in cancer treatment [9]
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