دورية أكاديمية
Precise pancreatic cancer therapy through targeted degradation of mutant p53 protein by cerium oxide nanoparticles
| العنوان: | Precise pancreatic cancer therapy through targeted degradation of mutant p53 protein by cerium oxide nanoparticles |
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| المؤلفون: | Hao Zhang, Wang Zhang, Bochuan Hu, Xiaohua Qin, Tianxiang Yi, Yayi Ye, Xiaowan Huang, Yang Song, Zhenyu Yang, Jieying Qian, Yunjiao Zhang |
| المصدر: | Journal of Nanobiotechnology, Vol 21, Iss 1, Pp 1-14 (2023) |
| بيانات النشر: | BMC, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Biotechnology LCC:Medical technology |
| مصطلحات موضوعية: | mutp53 degradation, CeO2 nanoparticles (CeO2 NPs), Ubiquitination proteasome, Cancer therapy, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5 |
| الوصف: | Abstract Background In a significant proportion of cancers, point mutations of TP53 gene occur within the DNA-binding domain, resulting in an abundance of mutant p53 proteins (mutp53) within cells, which possess tumor-promoting properties. A potential and straightforward strategy for addressing p53-mutated cancer involves the induction of autophagy or proteasomal degradation. Based on the previously reported findings, elevating oxidative state in the mutp53 cells represented a feasible approach for targeting mutp53. However, the nanoparticles previous reported lacked sufficient specificity of regulating ROS in tumor cells, consequently resulted in unfavorable toxicity in healthy cells. Results We here in showed that cerium oxide CeO2 nanoparticles (CeO2 NPs) exhibited an remarkable elevated level of ROS production in tumor cells, as compared to healthy cells, demonstrating that the unique property of CeO2 NPs in cancer cells provided a feasible solution to mutp53 degradation. CeO2 NPs elicited K48 ubiquitination-dependent degradation of wide-spectrum mutp53 proteins in a manner that was dependent on both the dissociation of mutp53 from the heat shock proteins Hsp90/70 and the increasing production of ROS. As expected, degradation of mutp53 by CeO2 NPs abrogated mutp53-manifested gain-of-function (GOF), leading to a reduction in cell proliferation and migration, and dramatically improved the therapeutic efficacy in a BxPC-3 mutp53 tumor model. Conclusions Overall, CeO2 NPs increasing ROS specifically in the mutp53 cancer cells displayed a specific therapeutic efficacy in mutp53 cancer and offered an effective solution to address the challenges posed by mutp53 degradation, as demonstrated in our present study. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1477-3155 |
| Relation: | https://doaj.org/toc/1477-3155 |
| DOI: | 10.1186/s12951-023-01867-6 |
| URL الوصول: | https://doaj.org/article/3aa186e145394e0c89aed63822b632e3 |
| رقم الأكسشن: | edsdoj.3aa186e145394e0c89aed63822b632e3 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 14773155 |
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| DOI: | 10.1186/s12951-023-01867-6 |