Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
Mol Med Rep. 2020 Aug;22(2):1213-1226. doi: 10.3892/mmr.2020.11240. Epub 2020 Jun 15.
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.
与癌症相关的慢性炎症的特征是产生不同类型的趋化因子和细胞因子。在癌症中，许多信号通路上调了几种细胞因子的表达水平，并使细胞进化为肿瘤状态。因此，通过抑制特定基因的表达来靶向这些信号通路是癌症治疗的主要目标。本研究探讨了天然多酚化合物棉酚（GOSS）在三阴性乳腺癌（TNBC）细胞中的抗癌作用，TNBC 是一种预后不良的最具侵袭性的乳腺癌类型。在两种 TNBC 细胞系 MDA-MB-231（MM-231）和 MDA-MB-468（MM-468）中检查了 GOSS 的作用，它们分别代表白种人和非裔美国人（AA）。获得的 IC50 表明，两种细胞系对该化合物的反应没有明显差异。然而，使用细胞因子测定的微阵列分析表明，GOSS 能够减弱两种细胞系中与癌症相关的细胞因子的表达水平。尽管 GOSS 没有改变 MM-468 细胞中 CCL2 的表达，但它能够使 TNF-α刺激的 MM-231 细胞的表达抑制 30%。此外，GOSS 处理不会改变 MM-231 细胞中的 IL-8 表达，但其在 TNF-α激活的 MM-468 细胞中的表达抑制了 60%。ELISA 测定支持微阵列数据，并表明 GOSS 抑制了 MM-231 细胞中 CCL2 的表达 40%，并抑制了 MM-468 细胞中 IL-8 的表达 50%。此外，在 MM-231 细胞中，GOSS 通过抑制 IKBKE、CCL2 和 MAPK1 基因的表达抑制 CCL2 的释放。此外，在 MM-468 细胞中，该化合物通过抑制 IL-8、MAPK1、MAPK3、CCDC88A、STAT3 和 PIK3CD 基因的表达来下调 IL-8 的释放。总之，本研究获得的数据表明，多酚化合物 GOSS 可能为 TNBC 治疗提供有价值的工具。
