Correlation of Reactive Oxygen Species Levels with Resveratrol Sensitivities of Anaplastic Thyroid Cancer Cells

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.

Potential Adverse Effects of Resveratrol: A Literature Review

“…However, as highlighted in the introduction, under certain conditions, an antioxidant may act as a pro-oxidant, leading to acceleration of lipid peroxidation and/or induction of DNA damage. In fact, RE could have pro-oxidant activities, rather than antioxidant activities, depending on RE concentration, RE form, treatment conditions, and time of treatment, as well as the type of cells used and their basal redox state [39,[98][99][100][101][102][103]. Interestingly, even chronobiology was shown to play a role in RE varying effects; when administered during the dark span, RE exerted an antioxidant effect by decreasing lipid peroxidation, whereas, during the light span, RE increased lipid peroxidation [39].…”

Health benefits of resveratrol administration

“…Many in vitro and in vivo studies suggest that resveratrol has anti-cancer properties due to its wide range of activities, including antioxidant effects and regulating the expression of pro-apoptotic proteins, as well as molecules underlying tumor development. Resveratrol is known to reduce the incidence and development of various types of cancer, such as cervical , pancreatic , gastric , breast and colorectal (Lucas et al, 2018), as well as thyroid cancer (Zheng et al, 2018). Research results indicate that resveratrol has protective effect on the normal cells, while inducing death in cancer cells.…”

“…Treatment of osteosarcoma cells with 20 μM resveratrol results in reduction of cell viability, decrease in self-renewing and tumorigenesis via inhibition of intracellular STAT3 signaling and cytokine synthesis (Peng & Jiang, 2018). In general, the anti-cancer activity of resveratrol is based on the suppression of the expression of proteins involved in carcinogenesis, such as phospholipid scramblase 1 , stimulation of caspase 3 cleavage (Lucas et al, 2018) and activation of the mitochondrial ROS signaling pathway (Zheng et al, 2018). Furthermore, resveratrol inhibits the cell cycle by inducing S-phase arrest in gastric cancer cells in a dose-dependent manner .…”

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

“…In fact, resveratrol stimulates apoptotic cell death through improving the oxidative phosphorylation [145]. The studies approve that the high concentration of resveratrol or long-term exposure to resveratrol is related to a perturbation in the oxidative-antioxidative balance leading to apoptotic cell death [146][147][148][149][150].…”