دورية أكاديمية
Carbidopa suppresses prostate cancer via aryl hydrocarbon receptor-mediated ubiquitination and degradation of androgen receptor
| العنوان: | Carbidopa suppresses prostate cancer via aryl hydrocarbon receptor-mediated ubiquitination and degradation of androgen receptor |
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| المؤلفون: | Chen, Zhiwei, Cai, Aimin, Zheng, Hailun, Huang, Huirong, Sun, Rui, Cui, Xiao, Ye, Weijian, Yao, Qing, Chen, Ruijie, Kou, Longfa |
| المصدر: | Oncogenesis ; volume 9, issue 5 ; ISSN 2157-9024 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cancer Research, Molecular Biology |
| الوصف: | Carbidopa, a peripheral decarboxylase inhibitor used with L-DOPA to treat Parkinson’s disease, has attracted significant interest in recent years for its anticancer effect. Increasing evidence reveals that Carbidopa can inhibit cancer cell growth and induce apoptosis through aryl hydrocarbon receptor (AHR) in some cancers. However, the antitumor effect of Carbidopa in prostate cancer (PCa) is not fully understood. Androgen receptor (AR) plays a central role in PCa, even in advanced “castrate-resistant” disease. In the present study, we report that Carbidopa suppresses the growth of PCa by downregulating the protein expression of AR. Carbidopa inhibits proliferation and migration of LNCaP cells and promotes apoptosis, but has no effect on the AR-independent prostate cell line DU145. Carbidopa increases ubiquitination of AR in LNCaP cells. Several studies have shown that AHR can act as an E3 ubiquitin ligase and promote the proteasomal degradation of AR. Quantitative RT-PCR, immunofluorescence staining and immunoblotting assay demonstrate that AHR is induced and activated by Carbidopa, and the co-immunoprecipitation assay shows that AR interacts with AHR, firmly confirming that Carbidopa decreases AR protein level though AHR-induced proteasomal degradation. In addition, Carbidopa suppresses PCa growth in vivo when xenografted into immunocompromised mice. Carbidopa treatment increases AHR protein level and decreases AR protein level in tumor tissues. Taken together, our study implicates Carbidopa for the first time in effective suppression of prostate cancer via a mechanism, involving AHR-mediated proteasomal degradation of AR. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41389-020-0236-x |
| الإتاحة: | https://doi.org/10.1038/s41389-020-0236-xTest https://www.nature.com/articles/s41389-020-0236-x.pdfTest https://www.nature.com/articles/s41389-020-0236-xTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.4DE7635D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41389-020-0236-x |
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