A macrolide from Streptomyces sp. modulates apoptosis and autophagy through Mcl‐1 downregulation in human breast cancer cells
| Autor: | Hao Yu Huang, Shih Jiuan Chiu, Jing Ru Weng, Chang Fang Chiu, Wei Yu Lin, Chia Hsien Feng, Jing Lan Hu, Li Yuan Bai |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Health
Toxicology and Mutagenesis Down-Regulation Apoptosis Breast Neoplasms 010501 environmental sciences Management Monitoring Policy and Law Toxicology 01 natural sciences 03 medical and health sciences 0302 clinical medicine Breast cancer Cell Line Tumor Autophagy medicine Humans Protein kinase B Cell Proliferation 0105 earth and related environmental sciences Cell growth Chemistry Cancer General Medicine medicine.disease Streptomyces Blot 030220 oncology & carcinogenesis Cancer cell MCF-7 Cells Cancer research Macrolides |
| Zdroj: | Environmental Toxicology. 36:1316-1325 |
| ISSN: | 1522-7278 1520-4081 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text