Abstract
Anaplastic thyroid carcinoma (ATC) is the most lethal thyroid malignancy without a reliable therapeutic agent. Resveratrol possesses cancer-suppressive effects, while its effect(s) on ATC cells remains unknown. Because oxidative damage caused by increased reactive oxygen species (ROS) is one of the therapeutic effects of anticancer drugs and oxidative stress-caused mitochondria swelling is observed in resveratrol-treated cancer cells, the oxidative statuses and their relevance with resveratrol sensitivities are elucidated using THJ-16T and THJ-11T ATC cells established from two human anaplastic thyroid carcinoma cases. The results revealed that resveratrol-treated THJ-16T rather than THJ-11T cells showed remarkable growth arrest and extensive apoptosis accompanied with the elevated ROS generation and the attenuated superoxide dismutase 2 (SOD2) and catalase (CAT) levels. Mitochondrial impairment and the enhanced caspase-9/caspase-3 activation are found only in resveratrol-sensitive THJ-16T cells. Treatment with the antioxidant N-acetylcysteine (NAC) partly attenuated resveratrol-induced ROS generation and apoptosis of THJ-16T cells. The levels of resveratrol metabolic enzymes (SULT1A1 and SULT1C2) in THJ-16T cells were lower than those in THJ-11T cells and therefore reversely related with resveratrol sensitivities of ATC cells. Our findings demonstrate the ability of resveratrol to increase ROS generation and oxidative-related cellular lesions in resveratrol-sensitive THJ-16T cells presumably through activating the ROS-mitochondrial signal pathway. The levels of SULTs and ROS may reflect the response manners of ATC cells to resveratrol.
Highlights
Anaplastic occurs in less than 2% of all thyroid cancers (TCs) but accounts for about 50% of TC-related death [1, 2]
We recently found that some THJ cell lines including those with retinoic acid resistance (THJ-16T and THJ-21T) were sensitive to resveratrol in terms of distinct growth arrest and extensive apoptosis, indicating the potential therapeutic values of this nontoxic polyphenol compound in the practical treatment of Anaplastic thyroid carcinoma (ATC) [10]
The effects of resveratrol on the proliferation of two ATC cells were elucidated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay (Figure 1(a))
Summary
Anaplastic occurs in less than 2% of all thyroid cancers (TCs) but accounts for about 50% of TC-related death [1, 2]. One major challenge to the current treatment modality for ATC is to explore a reliable therapeutic agent to suppress this extremely fast-growing and aggressive malignancy [4]. THJ cell lines were established in the Copland laboratory from different human anaplastic thyroid carcinoma tissues [9]. We recently found that some THJ cell lines including those with retinoic acid resistance (THJ-16T and THJ-21T) were sensitive to resveratrol in terms of distinct growth arrest and extensive apoptosis, indicating the potential therapeutic values of this nontoxic polyphenol compound in the practical treatment of ATCs [10]. The THJ-11T cell line had little response to resveratrol treatment due to certain unknown reason(s). It would be of clinical significance to investigate the underlying factors that influence resveratrol sensitivities of ATC cells
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