TY - JOUR AB - Chronic inflammation associated with cancer is characterized by the production of different types of chemokines and cytokines. In cancer, numerous signaling pathways upregulate the expression levels of several cytokines and evolve cells to the neoplastic state. Therefore, targeting these signaling pathways through the inhibition of distinctive gene expression is a primary target for cancer therapy. The present study investigated the anticancer effects of the natural polyphenol gossypol (GOSS) in triple‑negative breast cancer (TNBC) cells, the most aggressive breast cancer type with poor prognosis. GOSS effects were examined in two TNBC cell lines: MDA‑MB‑231 (MM‑231) and MDA‑MB‑468 (MM‑468), representing Caucasian Americans (CA) and African Americans (AA), respectively. The obtained IC50s revealed no significant difference between the two cell lines' response to the compound. However, the use of microarray assays for cytokine determination indicated the ability of GOSS to attenuate the expression levels of cancer‑related cytokines in the two cell lines. Although GOSS did not alter CCL2 expression in MM‑468 cells, it was able to cause 30% inhibition in TNF‑α‑stimulated MM‑231 cells. Additionally, IL‑8 was not altered by GOSS treatment in MM‑231 cells, while its expression was inhibited by 60% in TNF‑α‑activated MM‑468 cells. ELISA assays supported the microarray data and indicated that CCL2 expression was inhibited by 40% in MM‑231 cells, and IL‑8 expression was inhibited by 50% in MM‑468 cells. Furthermore, in MM‑231 cells, GOSS inhibited CCL2 release via the repression of IKBKE, CCL2 and MAPK1 gene expression. Additionally, in MM‑468 cells, the compound downregulated the release of IL‑8 through repressing IL‑8, MAPK1, MAPK3, CCDC88A, STAT3 and PIK3CD gene expression. In conclusion, the data obtained in the present study indicate that the polyphenol compound GOSS may provide a valuable tool in TNBC therapy. AD - Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA AU - Messeha,Samia ,S. AU - Zarmouh,Najla ,O. AU - Mendonca,Patricia AU - Cotton,Carolyn AU - Soliman,Karam ,F.A. DA - 2020/08/01 DO - 10.3892/mmr.2020.11240 EP - 1226 IS - 2 JO - Mol Med Rep KW - gossypol breast cancer gene expression CCL2 IL‑8 signaling pathways PY - 2020 SN - 1791-2997 1791-3004 SP - 1213 ST - Molecular mechanism of gossypol mediating CCL2 and IL‑8 attenuation in triple‑negative breast cancer cells T2 - Molecular Medicine Reports TI - Molecular mechanism of gossypol mediating CCL2 and IL‑8 attenuation in triple‑negative breast cancer cells UR - https://doi.org/10.3892/mmr.2020.11240 VL - 22 ER -