Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype. Non-available targeted therapy for TNBC represents its biggest treatment challenge. Thus, finding new promising effective drugs is urgently needed. In the present study, we investigated how berberine, a natural isoquinoline, impairs the survival of TNBC cells in both cellular and molecular levels. Our experimental model was based on the use of eight TNBC cell lines: MDA-MB-468, MDA-MB-231, HCC70, HCC38, HCC1937, HCC1143, BT-20, and BT-549. Berberine was cytotoxic against all treated TNBC cell lines. The most sensitive cell lines were HCC70 (IC50 = 0.19 µM), BT-20 (IC50 = 0.23 µM) and MDA-MB-468 (IC50 = 0.48 µM). Using flow cytometry techniques, berberine, at 0.5 and 1 µM for 120 and 144 h, not only induced cell cycle arrest, at G1 and/or G2/M phases, but it also triggered significant apoptosis. At the molecular level, these results are consistent with the expression of their related proteins using Western blot assays. Interestingly, while berberine was cytotoxic against TNBC cells, it had no effect on the viability of normal human breast cells MCF10A cultured in a 3D matrigel model. These results suggest that berberine may be a good potential candidate for TNBC drug development.

中文翻译：

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小檗碱损害三阴性乳腺癌细胞的存活：细胞和分子分析

三阴性乳腺癌 (TNBC) 是一种侵袭性乳腺癌亚型。TNBC 不可用的靶向治疗是其最大的治疗挑战。因此，迫切需要寻找新的有前景的有效药物。在本研究中，我们调查了小檗碱（一种天然异喹啉）如何在细胞和分子水平上损害 TNBC 细胞的存活。我们的实验模型基于使用八种 TNBC 细胞系：MDA-MB-468、MDA-MB-231、HCC70、HCC38、HCC1937、HCC1143、BT-20 和 BT-549。小檗碱对所有处理过的 TNBC 细胞系都具有细胞毒性。最敏感的细胞系是 HCC70 (IC50 = 0.19 µM)、BT-20 (IC50 = 0.23 µM) 和 MDA-MB-468 (IC50 = 0.48 µM)。使用流式细胞术技术，小檗碱在 0.5 和 1 µM 下持续 120 和 144 小时，不仅在 G1 和/或 G2/M 期诱导细胞周期停滞，但它也引发了显着的细胞凋亡。在分子水平上，这些结果与使用蛋白质印迹分析的相关蛋白质的表达一致。有趣的是，虽然小檗碱对 TNBC 细胞具有细胞毒性，但它对在 3D 基质胶模型中培养的正常人乳腺细胞 MCF10A 的活力没有影响。这些结果表明小檗碱可能是 TNBC 药物开发的良好潜在候选者。