A macrolide from Streptomyces sp. modulates apoptosis and autophagy through Mcl‐1 downregulation in human breast cancer cells. Issue 7 (13th March 2021)

• Record Type: Journal Article
• Authors: Chiu, Chang‐Fang; Chiu, Shih‐Jiuan; Bai, Li‐Yuan; Feng, Chia‐Hsien; Hu, Jing‐Lan; Lin, Wei‐Yu; Huang, Hao‐Yu; Weng, Jing‐Ru
• Is Part Of: Environmental toxicology. Volume 36:Issue 7(2021)
• Page Start: 1316
• Page End: 1325
• Publication Date: 2021-03-13
• Subjects: apoptosis -- autophagy -- JBIR‐100 -- macrolide -- mcl‐1; Water quality bioassay -- Periodicals; Water -- Pollution -- Toxicology -- Periodicals; Microbiological assay -- Periodicals; Toxicity testing -- Periodicals; Environmental toxicology -- Periodicals; Environmental Pollution -- Periodicals; Environmental Pollutants -- Periodicals; Environmental Monitoring -- Periodicals; Écotoxicologie -- Périodiques; Pollution -- Périodiques; 615.902
• DOI: 10.1002/tox.23128
• Languages: English
• ISSNs: 1520-4081

Abstract

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.