دورية أكاديمية
The development of an anti-cancer peptide M1-21 targeting transcription factor FOXM1
| العنوان: | The development of an anti-cancer peptide M1-21 targeting transcription factor FOXM1 |
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| المؤلفون: | Haojie Cheng, Jie Yuan, Chaozhu Pei, Min Ouyang, Huitong Bu, Yan Chen, Xiaoqin Huang, Zhenwang Zhang, Li Yu, Yongjun Tan |
| المصدر: | Cell & Bioscience, Vol 13, Iss 1, Pp 1-16 (2023) |
| بيانات النشر: | BMC, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Biotechnology LCC:Biology (General) LCC:Biochemistry |
| مصطلحات موضوعية: | M1-21, D-retro-inverso (DRI) peptide, Transcription factor FOXM1, Interfering peptide, Cancer treatment, Biotechnology, TP248.13-248.65, Biology (General), QH301-705.5, Biochemistry, QD415-436 |
| الوصف: | Abstract Background Transcription factor FOXM1 is a potential target for anti-cancer drug development. An interfering peptide M1-21, targeting FOXM1 and FOXM1-interacting proteins, is developed and its anti-cancer efficacy is evaluated. Methods FOXM1 C-terminus-binding peptides are screened by in silico protocols from the peptide library of FOXM1 (1-138aa) and confirmed by cellular experiments. The selected peptide is synthesized into its D-retro-inverso (DRI) form by fusing a TAT cell-penetrating sequence. Anti-cancer activities are evaluated in vitro and in vivo with tumor-grafted nude mice, spontaneous breast cancer mice, and wild-type metastasis-tracing mice. Anti-cancer mechanisms are analyzed. Distribution and safety profiles in mice are evaluated. Results With improved stability and cell inhibitory activity compared to the parent peptide, M1-21 binds to multiple regions of FOXM1 and interferes with protein-protein interactions between FOXM1 and its various known partner proteins, including PLK1, LIN9 and B-MYB of the MuvB complex, and β-catenin. Consequently, M1-21 inhibits FOXM1-related transcriptional activities and FOXM1-mediated nuclear importation of β-catenin and β-catenin transcriptional activities. M1-21 inhibits multiple types of cancer (20 µM in vitro or 30 mg/kg in vivo) by preventing proliferation, migration, and WNT signaling. Distribution and safety profiles of M1-21 are favorable (broad distribution and > 15 h stability in mice) and the tested non-severely toxic dose reaches 200 mg/kg in mice. M1-21 also has low hemolytic toxicity and immunogenicity in mice. Conclusions M1-21 is a promising interfering peptide targeting FOXM1 for the development of anti-cancer drugs. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-3701 |
| العلاقة: | https://doaj.org/toc/2045-3701Test |
| DOI: | 10.1186/s13578-023-01059-7 |
| الوصول الحر: | https://doaj.org/article/46473a34bc0c41efac564aa39bbbf70dTest |
| رقم الانضمام: | edsdoj.46473a34bc0c41efac564aa39bbbf70d |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20453701 |
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| DOI: | 10.1186/s13578-023-01059-7 |