دورية أكاديمية
Heterochiral dipeptide d-phenylalanyl- l-phenylalanine (H- D Phe- L Phe-OH) as a potential inducer of metastatic suppressor NM23H1 in p53 wild-type and mutant cells.
العنوان: | Heterochiral dipeptide d-phenylalanyl- l-phenylalanine (H- D Phe- L Phe-OH) as a potential inducer of metastatic suppressor NM23H1 in p53 wild-type and mutant cells. |
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المؤلفون: | Faheem MM; Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, Jammu and Kashmir, India.; School of Biotechnology, University of Jammu, Jammu, Jammu and Kashmir, India., Rahim JU; Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, Jammu and Kashmir, India.; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India., Ahmad SM; Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, Jammu and Kashmir, India.; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India., Mir KB; Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, Jammu and Kashmir, India.; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India., Kaur G; Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, Jammu and Kashmir, India.; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India., Bhagat M; School of Biotechnology, University of Jammu, Jammu, Jammu and Kashmir, India., Rai R; Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, Jammu and Kashmir, India.; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India., Goswami A; Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, Jammu and Kashmir, India.; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India. |
المصدر: | Molecular carcinogenesis [Mol Carcinog] 2022 Dec; Vol. 61 (12), pp. 1143-1160. Date of Electronic Publication: 2022 Oct 14. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8811105 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-2744 (Electronic) Linking ISSN: 08991987 NLM ISO Abbreviation: Mol Carcinog Subsets: MEDLINE |
أسماء مطبوعة: | Publication: <2005- > : [Hoboken, N.J.] : Wiley-Liss Original Publication: New York : Alan R. Liss, Inc., c1988- |
مواضيع طبية MeSH: | Tumor Suppressor Protein p53*/genetics , Tumor Suppressor Protein p53*/metabolism , Neoplasms*, Mice ; Animals ; Dipeptides/pharmacology ; Dipeptides/metabolism ; Phenylalanine/pharmacology ; Cell Line ; Cell Line, Tumor |
مستخلص: | In recent years, significant progress has been made to the use-case of small peptides because of their diversified edifice and hence their versatile application scope in cancer therapy. Here we identify the heterochiral dipeptide H- D Phe- L Phe-OH (F1) as a potent inducer of the metastatic suppressor NM23H1. We divulge the effect of F1 on the major EMT/metastasis-associated genes and the implications on the invasion and migration ability of cancer cells. The anti-invasive potential of F1 was directly correlated with NM23H1 expression. Mechanistically, F1 treatment elevated p53 levels as validated by localization and transcriptional studies. In the NM23H1 knockdown condition, F1 failed to induce any p53 expression/nuclear localization, indicating that the upregulation in p53 expression by F1 is NM23H1 dependent. We also demonstrate how the antimetastatic potential of F1 is primarily mediated through NM23H1 irrespective of the p53 status of the cell. However, both NM23H1 and a functional p53 protein in conjunction govern the apoptotic and cytostatic potential of F1. Coimmunoprecipitation studies unraveled the augmentation of the p53 and NM23H1 interaction in p53 wild-type cells. However, in p53 mutated cells, no such enrichment was evidenced. We employed mouse isogenic cell lines (4T-1 and 4T-1 p53) to determine the in vivo efficacy of F1 (spontaneous and experimental models). Decreased tumor volume in the cohort injected with 4T-1 p53 cells demonstrated that while the antimetastatic potential of F1 was reliant on NM23H1, p53 activation was required for ablation of primary tumor burden. Our findings unravel that F1 treatment induces significant abrogation of the migration, invasion and metastatic potential of both p53 wild-type and p53 deficient cancers mediated through NM23H1. (© 2022 Wiley Periodicals LLC.) |
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فهرسة مساهمة: | Keywords: NM23H1; epithelial to mesenchymal transition (EMT); heterochiral peptides; metastasis; metastasis suppressors; p53 |
المشرفين على المادة: | 0 (Tumor Suppressor Protein p53) 0 (Dipeptides) 47E5O17Y3R (Phenylalanine) |
تواريخ الأحداث: | Date Created: 20221014 Date Completed: 20221108 Latest Revision: 20221216 |
رمز التحديث: | 20231215 |
DOI: | 10.1002/mc.23465 |
PMID: | 36239557 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1098-2744 |
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DOI: | 10.1002/mc.23465 |