Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, Pennsylvania.
J Cell Physiol. 2019 Jul;234(7):11103-11118. doi: 10.1002/jcp.27761. Epub 2018 Nov 27.
Women with the breast cancer type 1 susceptibility protein (BRCA1) mutation and loss of BRCA1 expression are reported to have an increased risk of triple-negative breast cancer (TNBC). Targeting BRCA1 modulation might offer a therapeutic option to treat TNBC patients. Our studies detected that BRCA1 is poorly expressed in TNBC cell lines and highly expressed in ER breast cancer cell lines. To modulate BRCA1 expression, we tested two different dietary components to find out if any would induce tumor suppressor genes. We detected that quercetin and curcumin dose-dependently enhanced the BRCA1 expression. Further, a synergistic action of quercetin and curcumin was observed in modulating the BRCA1 level and in inhibiting the cell survival and migration of TNBC cell lines. Quercetin and curcumin appeared to induce BRCA1 promoter histone acetylation. Furthermore, BRCA1 knockdown induced cell survival and cell migration in ER cells were significantly decreased by the combined treatment of quercetin and curcumin. Our present study concluded that the combination treatment of quercetin and curcumin acts synergistically to induce anticancer activity against TNBC cells by modulating tumor suppressor genes.
据报道,携带乳腺癌 1 型易感性蛋白 (BRCA1) 突变和 BRCA1 表达缺失的女性患三阴性乳腺癌 (TNBC) 的风险增加。靶向 BRCA1 调节可能为治疗 TNBC 患者提供一种治疗选择。我们的研究检测到 BRCA1 在 TNBC 细胞系中表达水平较低,而在 ER 乳腺癌细胞系中表达水平较高。为了调节 BRCA1 的表达,我们测试了两种不同的膳食成分,以确定是否有任何成分可以诱导肿瘤抑制基因。我们发现槲皮素和姜黄素呈剂量依赖性地增强 BRCA1 的表达。此外,我们还观察到槲皮素和姜黄素在调节 BRCA1 水平以及抑制 TNBC 细胞系的细胞存活和迁移方面具有协同作用。槲皮素和姜黄素似乎诱导 BRCA1 启动子组蛋白乙酰化。此外,BRCA1 敲低可诱导 ER 细胞的细胞存活和迁移,而槲皮素和姜黄素的联合治疗可显著降低这种作用。我们的研究结论是,槲皮素和姜黄素的联合治疗通过调节肿瘤抑制基因,对 TNBC 细胞发挥协同抗癌作用。