A macrolide from Streptomyces sp. modulates apoptosis and autophagy through Mcl-1 downregulation in human breast cancer cells.

Abstract

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.