Academic Journal
NPS-2143 inhibit glioma progression by suppressing autophagy through mediating AKT-mTOR pathway.
| Τίτλος: | NPS-2143 inhibit glioma progression by suppressing autophagy through mediating AKT-mTOR pathway. |
|---|---|
| Συγγραφείς: | Nie JL; Department of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guiyang, P.R. China.; College of Pharmacy, Guizhou Medical University, Guiyang, P.R. China., Li Q; Department of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guiyang, P.R. China.; College of Pharmacy, Guizhou Medical University, Guiyang, P.R. China., Yin HT; Department of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guiyang, P.R. China.; College of Pharmacy, Guizhou Medical University, Guiyang, P.R. China., Yang JH; Department of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guiyang, P.R. China.; College of Pharmacy, Guizhou Medical University, Guiyang, P.R. China., Li M; Department of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guiyang, P.R. China.; College of Pharmacy, Guizhou Medical University, Guiyang, P.R. China., Li Q; Centre of Clinical Trials, Affiliated Hospital of Guizhou Medical University, Guiyang, P.R. China., Fan XH; Department of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guiyang, P.R. China.; College of Pharmacy, Guizhou Medical University, Guiyang, P.R. China., Zhao QQ; Clinical Research Center, Affiliated Hospital of Guizhou Medical University, Guiyang, P.R. China., Wen ZP; Department of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guiyang, P.R. China.; College of Pharmacy, Guizhou Medical University, Guiyang, P.R. China. |
| Πηγή: | Journal of cellular and molecular medicine [J Cell Mol Med] 2024 Apr; Vol. 28 (7), pp. e18221. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101083777 Publication Model: Print Cited Medium: Internet ISSN: 1582-4934 (Electronic) Linking ISSN: 15821838 NLM ISO Abbreviation: J Cell Mol Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford, England : Wiley-Blackwell Original Publication: Bucharest : "Carol Davila" University Press, 2000- |
| Ιατρικοί όροι (MeSH): | Glioma*/drug therapy , Glioma*/genetics , Glioma*/metabolism , Proto-Oncogene Proteins c-akt*/metabolism , Naphthalenes*/pharmacology, RNA, Messenger/genetics ; TOR Serine-Threonine Kinases/metabolism ; Animals ; Humans ; Mice ; Apoptosis ; Autophagy ; Cell Line, Tumor ; Cell Proliferation ; Mice, Nude |
| Περίληψη: | Gliomas are the most common tumours in the central nervous system. In the present study, we aimed to find a promising anti-glioma compound and investigate the underlying molecular mechanism. Glioma cells were subjected to the 50 candidate compounds at a final concentration of 10 μM for 72 h, and CCK-8 was used to evaluate their cytotoxicity. NPS-2143, an antagonist of calcium-sensing receptor (CASR), was selected for further study due to its potent cytotoxicity to glioma cells. Our results showed that NPS-2143 could inhibit the proliferation of glioma cells and induce G1 phase cell cycle arrest. Meanwhile, NPS-2143 could induce glioma cell apoptosis by increasing the caspase-3/6/9 activity. NPS-2143 impaired the immigration and invasion ability of glioma cells by regulating the epithelial-mesenchymal transition process. Mechanically, NPS-2143 could inhibit autophagy by mediating the AKT-mTOR pathway. Bioinformatic analysis showed that the prognosis of glioma patients with low expression of CASR mRNA was better than those with high expression of CASR mRNA. Gene set enrichment analysis showed that CASR was associated with cell adhesion molecules and lysosomes in glioma. The nude mice xenograft model showed NPS-2143 could suppress glioma growth in vivo. In conclusion, NPS-2143 can suppress the glioma progression by inhibiting autophagy. (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.) |
| References: | Int J Mol Sci. 2020 Oct 15;21(20):. (PMID: 33076271) Semin Cancer Biol. 2022 Jul;82:162-175. (PMID: 33640445) Pharmacol Rev. 2020 Jul;72(3):558-604. (PMID: 32467152) Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102. (PMID: 28407145) Int J Mol Sci. 2021 Sep 19;22(18):. (PMID: 34576291) Ecotoxicol Environ Saf. 2020 Feb;189:110052. (PMID: 31830606) Cell Mol Life Sci. 2022 Jul 5;79(8):398. (PMID: 35790583) Sci Adv. 2021 Jan 15;7(3):. (PMID: 33523897) J Cell Mol Med. 2024 Apr;28(7):e18221. (PMID: 38509759) Nat Rev Endocrinol. 2018 Dec;15(1):33-51. (PMID: 30443043) World J Gastroenterol. 2018 Sep 28;24(36):4119-4131. (PMID: 30271078) Drug Resist Updat. 2015 Mar;19:1-12. (PMID: 25791797) Int J Mol Med. 2021 Jan;47(1):302-314. (PMID: 33416112) J Exp Clin Cancer Res. 2018 Sep 12;37(1):225. (PMID: 30208924) Cell. 2008 Jan 11;132(1):27-42. (PMID: 18191218) J Pharmacol Sci. 2019 Mar;139(3):254-257. (PMID: 30808588) Front Oncol. 2020 Feb 05;10:69. (PMID: 32117726) Lancet Oncol. 2016 Nov;17(11):1521-1532. (PMID: 27686946) Neuro Oncol. 2014 Jan;16(2):179-90. (PMID: 24305703) J Exp Clin Cancer Res. 2019 Jul 10;38(1):298. (PMID: 31291988) Autophagy. 2021 May;17(5):1077-1095. (PMID: 32401642) Clin Cancer Res. 2019 Jun 15;25(12):3602-3616. (PMID: 30862693) Cell Calcium. 2019 Sep;82:102051. (PMID: 31276858) Int J Mol Sci. 2018 Sep 22;19(10):. (PMID: 30248992) Cold Spring Harb Perspect Biol. 2015 Jan 05;7(1):a020412. (PMID: 25561720) Nat Rev Cancer. 2017 Sep;17(9):528-542. (PMID: 28751651) Mol Cancer. 2021 Oct 4;20(1):128. (PMID: 34607583) Mol Cancer. 2020 Jan 22;19(1):12. (PMID: 31969156) Mol Cancer. 2014 Feb 28;13:42. (PMID: 24576174) Mol Cell. 2007 Jan 26;25(2):193-205. (PMID: 17244528) Genes Dis. 2016 May 11;3(3):198-210. (PMID: 30258889) Acta Pharmacol Sin. 2021 Jan;42(1):1-9. (PMID: 32152439) Nat Cell Biol. 2020 Jan;22(1):97-107. (PMID: 31907411) Biochem Biophys Res Commun. 2020 Oct 1;530(4):651-657. (PMID: 32768195) Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3585-3594. (PMID: 30251678) Neuro Oncol. 2021 Aug 2;23(8):1231-1251. (PMID: 34185076) Cell. 2018 Apr 5;173(2):291-304.e6. (PMID: 29625048) J Neuroimmune Pharmacol. 2006 Sep;1(3):223-36. (PMID: 18040800) Nat Rev Clin Oncol. 2018 Dec;15(12):731-747. (PMID: 30333516) Nat Rev Mol Cell Biol. 2013 Aug;14(8):518-28. (PMID: 23877564) |
| Grant Information: | ZK [2021] General-563 Guizhou Provincial Science and Technology Projects; 82060667 National Natural Science Foundation of China; gyfynsfc [2020]-34 The Cultivate Project 2020 for National Natural Science Foundation of China, Affiliated Hospital of Guizhou Medical University |
| Contributed Indexing: | Keywords: GSEA; NPS‐2143; autophagy; chemotherapy; glioma |
| Substance Nomenclature: | 0 (N-(2-hydroxy-3-(2-cyano-3-chlorophenoxy)propyl)-1,1-dimethyl-2-(2-nephthyl)ethylamine) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) 0 (RNA, Messenger) EC 2.7.11.1 (TOR Serine-Threonine Kinases) 0 (Naphthalenes) |
| Entry Date(s): | Date Created: 20240321 Date Completed: 20240322 Latest Revision: 20240716 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10955153 |
| DOI: | 10.1111/jcmm.18221 |
| PMID: | 38509759 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1582-4934 |
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| DOI: | 10.1111/jcmm.18221 |