Quercetin Induces Anticancer Activity by Upregulating Pro-NAG-1/GDF15 in Differentiated Thyroid Cancer Cells

Abstract

Although the treatment of thyroid cancer has improved, unnecessary surgeries are performed due to a lack of specific diagnostic and prognostic markers. Therefore, the identification of novel biomarkers should be considered in the diagnosis and treatment of thyroid cancer. In this study, antibody arrays were performed using tumor and adjacent normal tissues of patients with papillary thyroid cancer, and several potential biomarkers were identified. Among the candidate proteins chosen based on the antibody array data, mature NAG-1 exhibited increased expression in tumor tissues compared to adjacent normal tissues. In contrast, pro-NAG-1 expression increased in normal tissues, as assessed by western blot analysis. Furthermore, pro-NAG-1 expression was increased when the thyroid cancer cells were treated with phytochemicals and nonsteroidal anti-inflammatory drugs in a dose-dependent manner. In particular, quercetin highly induced the expression of pro-NAG-1 but not that of mature NAG-1, with enhanced anticancer activity, including apoptosis induction and cell cycle arrest. Examination of the NAG-1 promoter activity showed that p53, C/EBPα, or C/EBPδ played a role in quercetin-induced NAG-1 expression. Overall, our study indicated that NAG-1 may serve as a novel biomarker for thyroid cancer prognosis and may be used as a therapeutic target for thyroid cancers.

PLGA-Quercetin Nano-Formulation Inhibits Cancer Progression via Mitochondrial Dependent Caspase-3,7 and Independent FoxO1 Activation with Concomitant PI3K/AKT Suppression

“…Quercetin, a known phytochemical has diverse biological actions including antioxidant properties, anti-inflammatory, antimicrobial, and anticancer activities [ 5 ]. Quercetin is also useful in treating diabetes, bladder infections, arthritis, and heart problems.…”

Interpreting the Pharmacological Mechanisms of Sho-saiko-to on Thyroid Carcinoma through Combining Network Pharmacology and Experimental Evaluation

“…Furthermore, quercetin could also down-regulate the expression of Hsp90 and inhibit chymotrypsin-like proteasome activity, inducing the inhibition of cell viability and proliferation and caspase-dependent apoptotic in papillary thyroid cancer cells. 24 Interestingly, quercetin could enhance the inhibitory effects of sorafenib on the growth and migration of thyroid cancer cells, 25 which meat that synergistic treatment of Sho-saiko-to and other chemotherapy regimens might has broader application prospects.…”

“…Furthermore, quercetin could also downregulate the expression of Hsp90 and inhibit chymotrypsinlike proteasome activity, inducing the inhibition of cell viability and proliferation and caspase-dependent apoptotic in papillary thyroid cancer cells. 24 Interestingly, quercetin could enhance the inhibitory effects of sorafenib on the growth and migration of thyroid cancer cells, 25 which meat that synergistic treatment of Sho-saiko-to and other chemotherapy regimens might has broader application prospects. In addition, we also built a PPI network and obtained the top 20 genes of Sho-saiko-to against thyroid cancer (AKT1, MAPK3, STAT3, MAPK1, JUN, TP53, MAPK14, FOS, EGFR, RELA, IL6, ESR1, VEGFA, CTNNB1, MYC, NR3C1, MAPK8, RXRA, TNF, EGF, NCOA1) by degree value.…”

Recent updates on anticancer mechanisms of polyphenols

“…In HCT116 colon carcinoma cells, apoptosis of the tumor cells is caused by p53 to the quercetin-mediated expression of NAG-1 ( Gibellini et al, 2011 ). However, a recent study has revealed that quercetin induces apoptosis through only pro-NAG-1 expression; however, mature NAG-1 did not induce apoptosis which was mediated by the C/EBP transcription factor in thyroid cancer cell lines ( Hong et al, 2021a ) ( Table 1 ).…”