Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
Cancer Center, China Medical University Hospital, Taichung, Taiwan.
Environ Toxicol. 2021 Jul;36(7):1316-1325. doi: 10.1002/tox.23128. Epub 2021 Mar 13.
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.
海洋生物中的次生代谢产物具有多种针对疾病（如癌症）的药理活性。在这项研究中，研究人员从链霉菌属中分离得到的大环内酯 JBIR-100 对乳腺癌细胞的抗增殖作用进行了研究。结果表明，JBIR-100 对 MCF-7 和 MDA-MB-231 乳腺癌细胞的生长具有浓度和时间依赖性的抑制作用。通过半胱天冬酶激活和 PARP 裂解，证实 JBIR-100 诱导了细胞凋亡。Western blot 分析显示，JBIR-100 调节了 Akt/NF-κB 信号通路组成部分和 Bcl-2 家族成员的表达。Mcl-1 的过表达部分挽救了 JBIR-100 诱导的 MCF-7 细胞的细胞毒性。此外，透射电子显微镜分析、共聚焦分析和 Western blot 分析表明，JBIR-100 抑制了 MCF-7 细胞中的自噬。自噬抑制剂的暴露并没有增强 JBIR-100 诱导的细胞凋亡。综上所述，这些结果表明，JBIR-100 可能可用于乳腺癌的治疗。
