Quercetin inhibition of TNFα‐induced CCL28 release from human triple negative breast cancer (MDA‐MB‐468) cells

Abstract

Quercetin is a natural chemopreventative flavonoid found in fruits, vegetables, and herbs, which exerts antitumor, antiinflammatory, and antioxidant effects. A hallmark of cancer is the recruitment of regulatory T cells (Tregs), which promotes hypoxia‐driven angiogenesis. In this study, we evaluated the effects of quercetin on the attenuation of the release of tumor necrosis factor‐alpha (TNF‐α)‐induced tumor promoting chemokines in MDA‐MB‐468 triple negative breast cancer cells, with a focus on those associated with Tregs recruitment. Initial studies were performed using antibody microarrays which specifically show that TNF‐α (40ng/mL)‐induced protein expression of CNTF, IGFBP‐1, IL‐5, IL‐6, PARC, TNF‐beta, BTC, CCL28, GITR, GRO, GRO‐alpha, HCC‐4, IL‐8, oncostatin M, sTNF‐RI, VEGR‐D, were downregulated by a sublethal concentration of quercetin (40μM). Furthermore, the obtained data show that quercetin downregulated TNF‐α‐induced CCL28 release by 60% as it was further validated by ELISA. To date, there is little known about the presence of CCL28 in breast cancer. These findings suggest that quercetin can modulate CCL28 release and inhibit the recruitment of Tregs, a pivotal factor in tumor cell growth.Support or Funding InformationThis research was supported by the National Institute for Minority Health and Health Disparities of the National Institutes of Health through Grant Number G12 MD007582 and Grant Number P20 MD006738.