Secondary metabolites in marine organisms exhibit various pharmacological activities against diseases, such as cancer. In this study, the anti-proliferative effect of JBIR-100, a macrolide isolated from Streptomyces sp., was investigated in breast cancer cells. Cell growth was inhibited in response to JBIR-100 treatment concentration- and time-dependently in both MCF-7 and MDA-MB-231 breast cancer cells. JBIR-100 caused apoptosis, as verified by caspase activation and the cleavage of PARP. Western blotting revealed that JBIR-100 modulated the expression of Akt/NF-κB signaling components and Bcl-2 family members. Overexpression of Mcl-1 partially rescued MCF-7 cells from JBIR-100-induced cytotoxicity. In addition, transmission electron microscopy analyses, confocal analysis, and western blot assay indicated that JBIR-100 inhibited autophagy in MCF-7 cells. Exposure to the autophagy inhibitor did not synergize JBIR-100-induced apoptosis. In summary, our results suggested that JBIR-100 may be potentially used for breast cancer therapy.

中文翻译：

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来自链霉菌属的大环内酯。通过人乳腺癌细胞中的 Mcl-1 下调调节细胞凋亡和自噬

海洋生物中的次级代谢产物对疾病（如癌症）表现出多种药理活性。在这项研究中，JBIR-100（一种从链霉菌中分离的大环内酯）的抗增殖作用sp.，在乳腺癌细胞中进行了研究。在 MCF-7 和 MDA-MB-231 乳腺癌细胞中，JBIR-100 处理浓度和时间依赖性地抑制细胞生长。JBIR-100 引起细胞凋亡，这已通过半胱天冬酶激活和 PARP 的裂解得到证实。蛋白质印迹显示 JBIR-100 调节 Akt/NF-κB 信号成分和 Bcl-2 家族成员的表达。Mcl-1 的过表达部分挽救了 MCF-7 细胞免受 JBIR-100 诱导的细胞毒性。此外，透射电子显微镜分析、共聚焦分析和蛋白质印迹分析表明 JBIR-100 抑制 MCF-7 细胞中的自噬。暴露于自噬抑制剂不会协同 JBIR-100 诱导的细胞凋亡。总之，我们的结果表明 JBIR-100 可能用于乳腺癌治疗。