| Autor: |
Yidan Liang, Lai Yi, Ping Deng, Liting Wang, Yang Yue, Hui Wang, Li Tian, Jia Xie, Mengyan Chen, Yan Luo, Zhengping Yu, Huifeng Pi, Zhou Zhou |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Ecotoxicology and Environmental Safety, Vol 224, Iss , Pp 112626- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
0147-6513 |
| DOI: |
10.1016/j.ecoenv.2021.112626 |
| Popis: |
Cadmium (Cd) is a carcinogen that stimulates breast cancer (BC) progression. Rapamycin is a macrolide antibiotic produced by Streptomyces hygroscopicus that possesses a wide array of pharmacological activities, including anti-BC activity. However, the effects of rapamycin on Cd-increased BC progression and the underlying mechanism have not been fully elucidated. Here, we hypothesize that rapamycin antagonizes Cd-induced BC cell proliferation and metastasis by directly modulating ACSS2. In this study, we found that rapamycin efficiently inhibited Cd-induced proliferation, invasion and migration in MCF-7 and T47-D cells. Moreover, a surface plasmon resonance (SPR) assay confirmed that rapamycin directly binds to the ACSS2 protein with a calculated equilibrium dissociation constant (KD) of 18.3 μM. Molecular docking showed that there are three binding sites in the ACSS2 protein and that rapamycin binds at the coenzyme A (COA) binding site with a docking score of − 12.26 and a binding free energy of − 26.34 kcal/mol. More importantly, rapamycin suppresses Cd-induced BC progression by activating ACSS2. After cells were cotreated with an ACSS2 inhibitor, the effects of rapamycin were abolished. In conclusion, our findings suggest that rapamycin suppresses Cd-augmented BC progression by upregulating ACSS2, and ACSS2 may serve as a direct target of rapamycin for inhibiting xenobiotic (e.g., Cd)-mediated BC progression. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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