Effects of the Bioflavonoid Quercetin on TLR4 Expression and NFKb activation in A375 Melanoma Cells

Early research indicates that quercetin, a bioflavonoid, seems to limit cancer progression through the down regulation of toll‐like receptor 4 (TLR4). Many cancers, including melanoma, upregulate expression of TLR4 which appears to be associated with cell survival and proliferation. The purpose of this study is to examine TLR4 expression, downstream signaling and changes in target gene expression that may contribute to quercetin’s anti‐proliferative properties. Cells were treated with 100 uM quercetin, vehicle control (DMSO), or no treatment for 24 hours. NFKb activation was quantified by differential centrifugation of cytosolic and nuclear fractions of treated cells by immunoprecipitation and Western blotting. TLR4 was evaluated with immunoblotting. We found that quercetin treated cells had 15% higher NFKb nuclear fraction than the cells with no or vehicle only treatment. TLR4 was, however, effectively downregulated by quercetin treatment. These findings are similar to those seen pancreatic cancer and some other cell models. It appears that this bioflavonoid may have different targets and effects in different types of cancer cells, making it necessary to understand its differential mechanisms of action. Support or Funding Information Supported by the NIH Common Fund, through the Office of Strategic Coordination, Office of the NIH Director with the linked awards: TL4GM118992, RL5GM118990, UL1GM118991 and by Fort Lewis College MARC‐USTAR.