Abstract
In this study, we have investigated the antiproliferative effect of quercetin on human papillary thyroid cancer cells and determined the apoptotic mechanisms underlying its actions. We have used different concentrations of quercetin to induce apoptosis and measured cell viability. Apoptosis and cell cycle analysis was determined by flow cytometry using Annexin V and propidium iodide. Finally, we have measured changes in caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) protein expression levels as hallmarks of apoptosis and Hsp90 protein expression level as a marker of proteasome activity in treated and control cells. Quercetin treatment of human papillary thyroid cancer cells resulted in decreased cell proliferation and increased rate of apoptosis by caspase activation. Furthermore, it was demonstrated that quercetin induces cancer cell apoptosis by downregulating the levels of Hsp90. In conclusion, we have shown that quercetin induces downregulation of Hsp90 expression that may be involved in the decrease of chymotrypsin-like proteasome activity which, in order, induces inhibition of growth and causes cell death in thyroid cancer cells. Thus, quercetin appears to be a promising candidate drug for Hsp90 downregulation and apoptosis of thyroid cancer cells.
Highlights
Thyroid cancer represents 1% of all malignancies with papillary thyroid carcinoma forming the majority of cases [1]
Quercetin treatment downregulated the expression of Hsp90 in B-CPAP cells compared to controls. These results indicated that quercetin-induced cancer cell apoptosis may be related to the downregulation of Hsp90 levels
We have shown that quercetin inhibited papillary thyroid cancer cell proliferation and triggered apoptosis at 50 and 75 μM concentrations, but cells were arrested in the S phase only at 75 μM concentration
Summary
Thyroid cancer represents 1% of all malignancies with papillary thyroid carcinoma forming the majority of cases [1]. BCPAP is a papillary thyroid carcinoma cell line that is known to have BRAF V600E mutation. BRAF mutations occur in approximately 8% of human tumors and are widespread in papillary thyroid cancer (36–69%) [2, 3]. Cancer therapy aimed at MAPK signaling utilizes selective inhibitors of RAF and MEK kinases as well as inhibitors of the Hsp90 [4,5,6]. Hsp is a chaperone protein necessary for survival under stress conditions which regulates the stability and activity of oncogenic proteins [5]. It has been reported that inhibitors of Hsp may stimulate proteasomal degradation of mutant B-Raf proteins [6]
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