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.) |
| References: | Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca-Cancer J Clin. 2018;68(6):394-424. Welch DR, Hurst DR. Defining the hallmarks of metastasis. Cancer Res. 2019;79(12):3011-3027. Revenco T, Nicodème A, Pastushenko I, et al. Context dependency of epithelial-to-mesenchymal transition for metastasis. Cell Rep. 2019;29(6):1458-1468.e3. Mittal V. Epithelial mesenchymal transition in tumor metastasis. Annu Rev Pathol: Mech Dis. 2018;13:395-412. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 2010;29(34):4741-4751. Khan I, Steeg PS. Metastasis suppressors: functional pathways. Lab Investig. 2018;98(2):198-210. Mátyási B, Farkas Z, Kopper L, et al. The function of NM23-H1/NME1 and its homologs in major processes linked to metastasis. Pathol Oncol Res. 2020;26(1):49-61. Marino N, Nakayama J, Collins JW, Steeg PS. Insights into the biology and prevention of tumor metastasis provided by the Nm23 metastasis suppressor gene. Cancer Metastasis Rev. 2012;31(3):593-603. Guan-zhen Y, Ying C, Can-rong N, Guo-dong W, Jian-xin Q, Jie-jun W. Reduced protein expression of metastasis-related genes (nm23, KISS1, KAI1 and p53) in lymph node and liver metastases of gastric cancer. Int J Exp Pathol. 2007;88(3):175-183. Steeg PS, De La Rosa A, Flatow U, MacDonald NJ, Benedict M, Leone A. Nm23 and breast cancer metastasis. Breast Cancer Res Treat. 1993;25(2):175-187. Mccorkle JR, Leonard MK, Kraner SD, et al. The metastasis suppressor NME1 regulates expression of genes linked to metastasis and patient outcome in melanoma and breast carcinoma. Cancer Genom Proteom. 2014;11(4):175-194. Steeg PS, Horak CE, Miller KD. Clinical-translational approaches to the Nm23-H1 metastasis suppressor. Clin Cancer Res. 2008;14(16):5006-5012. Martinez JA, Prevot S, Nordlinger B, et al. Overexpression of nm23-H1 and nm23-H2 genes in colorectal carcinomas and loss of nm23-H1 expression in advanced tumour stages. Gut. 1995;37(5):712-720. Jung H, Seong H-A, Manoharan R, Ha H. Serine-threonine kinase receptor-associated protein inhibits apoptosis signal-regulating kinase 1 function through direct interaction. J Biol Chem. 2010;285(1):54-70. Jung H, Seong H-A, Ha H. NM23-H1 tumor suppressor and its interacting partner STRAP activate p53 function. J Biol Chem. 2007;282(48):35293-35307. Seong H-A, Jung H, Ha H. NM23-H1 tumor suppressor physically interacts with serine-threonine kinase receptor-associated protein, a transforming growth factor-β (TGF-β) receptor-interacting protein, and negatively regulates TGF-β signaling. J Biol Chem. 2007;282(16):12075-12096. Marino N, Marshall J-C, Steeg PS. Protein-protein interactions: a mechanism regulating the anti-metastatic properties of Nm23-H1. Naunyn-Schmiedeb Arch Pharmacol. 2011;384(4):351-362. Ryan KM, Phillips AC, Vousden KH. Regulation and function of the p53 tumor suppressor protein. Curr Opin Cell Biol. 2001;13(3):332-337. Soussi T. The p53 tumor suppressor gene: from molecular biology to clinical investigation. Ann N Y Acad Sci. 2000;910(1):121-139. Arruebo M, Vilaboa N, Sáez-Gutierrez B, et al. Assessment of the evolution of cancer treatment therapies. Cancers. 2011;3(3):3279-3330. Hoskin DW, Ramamoorthy A. Studies on anticancer activities of antimicrobial peptides. Biochim Biophys Acta, Biomembr. 2008;1778(2):357-375. Tyagi A, Tuknait A, Anand P, et al. CancerPPD: a database of anticancer peptides and proteins. Nucleic Acids Res. 2015;43(D1):D837-D843. Chen S, Gfeller D, Buth SA, Michielin O, Leiman PG, Heinis C. Improving binding affinity and stability of peptide ligands by substituting glycines with d-amino acids. ChemBioChem. 2013;14(11):1316-1322. Bai D, Yu S, Zhong S, et al.d-amino acid position influences the anticancer activity of galaxamide analogs: an apoptotic mechanism study. Int J Mol Sci. 2017;18(3):544. Hilchie AL, Haney EF, Pinto DM, Hancock RE, Hoskin DW. Enhanced killing of breast cancer cells by a d-amino acid analog of the winter flounder-derived pleurocidin NRC-03. Exp Mol Pathol. 2015;99(3):426-434. Pettersson M, Quant M, Min J, et al. Design, synthesis and evaluation of 2, 5-diketopiperazines as inhibitors of the MDM2-p53 interaction. PLoS One. 2015;10(10):e0137867. Shankar S, Faheem MM, Nayak D, et al. Cyclodipeptide c (orn-pro) conjugate with 4-ethylpiperic acid abrogates cancer cell metastasis through modulating mdm2. Bioconjug Chem. 2018;29(1):164-175. Kumar V, Dhanjal JK, Bhargava P, et al. Antitussive noscapine and antiviral drug conjugates as arsenal against COVID-19: a comprehensive chemoinformatics analysis. J Biomol Struct Dyn. 2020;40:1-16. Faheem MM, Rasool RU, Ahmad SM, et al. Par-4 mediated Smad4 induction in PDAC cells restores canonical TGF-β/Smad4 axis driving the cells towards lethal EMT. Eur J Cell Biol. 2020;99(4):151076. Wang W, Qin J-J, Voruganti S, et al. Identification of a new class of MDM2 inhibitor that inhibits growth of orthotopic pancreatic tumors in mice. Gastroenterology. 2014;147(4):893-902.e2. Jafari R, Almqvist H, Axelsson H, et al. The cellular thermal shift assay for evaluating drug target interactions in cells. Nat Protoc. 2014;9(9):2100-2122. Martin KH, Hayes KE, Walk EL, Ammer AG, Markwell SM, Weed SA. Quantitative measurement of invadopodia-mediated extracellular matrix proteolysis in single and multicellular contexts. J Vis Exp. 2012;(66):4119. Nayak D, Katoch A, Sharma D, et al. Indolylkojyl methane analogue IKM5 potentially inhibits invasion of breast cancer cells via attenuation of GRP78. Breast Cancer Res Treat. 2019;177(2):307-323. Jegham H, Roy J, Maltais R, Desnoyers S, Poirier D. A novel aminosteroid of the 5α-androstane-3α, 17β-diol family induces cell cycle arrest and apoptosis in human promyelocytic leukemia HL-60 cells. Invest New Drugs. 2012;30(1):176-185. Paschall AV, Liu K. An orthotopic mouse model of spontaneous breast cancer metastasis. J Vis Exp. 2016;114:e54040. Sang H, Pisarev VM, Chavez J, et al. Murine mammary adenocarcinoma cells transfected with p53 and/or Flt3L induce anti-tumor immune responses. Cancer Gene Ther. 2005;12(4):427-437. Zimmerman M, Hu X, Liu K. Experimental metastasis and CTL adoptive transfer immunotherapy mouse model. J Vis Exp. 2010;(45):e2077. Chakraborty S, Kumar A, Faheem MM, et al. Vimentin activation in early apoptotic cancer cells errands survival pathways during DNA damage inducer CPT treatment in colon carcinoma model. Cell Death Dis. 2019;10(6):1-16. Rasool RU, Nayak D, Chakraborty S, et al. Differential regulation of NM23-H1 under hypoxic and serum starvation conditions in metastatic cancer cells and its implication in EMT. Eur J Cell Biol. 2017;96(2):164-171. Moll UM, Petrenko O. The MDM2-p53 interaction. Mol Cancer Res. 2003;1(14):1001-1008. Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev. 2007;87(1):99-163. Karimian A, Ahmadi Y, Yousefi B. Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage. DNA Repair (Amst). 2016;42:63-71. Brosh R, Rotter V. When mutants gain new powers: news from the mutant p53 field. Nat Rev Cancer. 2009;9(10):701-713. Muller PA, Vousden KH. Mutant p53 in cancer: new functions and therapeutic opportunities. Cancer Cell. 2014;25(3):304-317. Yerlikaya A, Okur E, Ulukaya E. The p53-independent induction of apoptosis in breast cancer cells in response to proteasome inhibitor bortezomib. Tumor Biol. 2012;33(5):1385-1392. Apostolopoulos V, Matsoukas J, Plebanski M, Mavromoustakos T. Applications of peptide mimetics in cancer. Curr Med Chem. 2002;9(4):411-420. Dennison SR, Whittaker M, Harris F, Phoenix DA. Anticancer α-helical peptides and structure/function relationships underpinning their interactions with tumour cell membranes. Curr Protein Pept Sci. 2006;7(6):487-499. Zhong S, Bhattacharya S, Chan W, Jasti B, Li X. Leucine-aspartic acid-valine sequence as targeting ligand and drug carrier for doxorubicin delivery to melanoma cells: in vitro cellular uptake and cytotoxicity studies. Pharm Res. 2009;26(12):2578-2587. Iglesias S, Alvarez N, Torre MH, et al. Synthesis, structural characterization and cytotoxic activity of ternary copper (II)-dipeptide-phenanthroline complexes. A step towards the development of new copper compounds for the treatment of cancer. J Inorg Biochem. 2014;139:117-123. Marchesan S, Vargiu AV, Styan KE. The Phe-Phe motif for peptide self-assembly in nanomedicine. Molecules. 2015;20(11):19775-19788. Brabletz T, Kalluri R, Nieto MA, Weinberg RA. EMT in cancer. Nat Rev Cancer. 2018;18(2):128-134. |
| 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 |
Full Text Finder | تدمد: | 1098-2744 |
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| DOI: | 10.1002/mc.23465 |