Antitumoral Activity of the Universal Methyl Donor S -Adenosylmethionine in Glioblastoma Cells.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, c1995-

Glioblastoma*/drug therapy ; Glioblastoma*/metabolism ; Glioblastoma*/pathology ; S-Adenosylmethionine*/pharmacology ; Apoptosis*/drug effects ; Cell Proliferation*/drug effects ; Antineoplastic Agents*/pharmacology ; Antineoplastic Agents*/chemistry; Humans ; Cell Line, Tumor ; Cell Survival/drug effects ; DNA Repair/drug effects ; Aurora Kinase B/metabolism ; Aurora Kinase B/antagonists & inhibitors ; Brain Neoplasms/drug therapy ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Rad51 Recombinase/metabolism ; Cell Cycle Checkpoints/drug effects ; Mitosis/drug effects

Glioblastoma (GBM), the most frequent and lethal brain cancer in adults, is characterized by short survival times and high mortality rates. Due to the resistance of GBM cells to conventional therapeutic treatments, scientific interest is focusing on the search for alternative and efficient adjuvant treatments. S -Adenosylmethionine (AdoMet), the well-studied physiological methyl donor, has emerged as a promising anticancer compound and a modulator of multiple cancer-related signaling pathways. We report here for the first time that AdoMet selectively inhibited the viability and proliferation of U87MG, U343MG, and U251MG GBM cells. In these cell lines, AdoMet induced S and G2/M cell cycle arrest and apoptosis and downregulated the expression and activation of proteins involved in homologous recombination DNA repair, including RAD51, BRCA1, and Chk1. Furthermore, AdoMet was able to maintain DNA in a damaged state, as indicated by the increased γH2AX/H2AX ratio. AdoMet promoted mitotic catastrophe through inhibiting Aurora B kinase expression, phosphorylation, and localization causing GBM cells to undergo mitotic catastrophe-induced death. Finally, AdoMet inhibited DNA repair and induced cell cycle arrest, apoptosis, and mitotic catastrophe in patient-derived GBM cells. In light of these results, AdoMet could be considered a potential adjuvant in GBM therapy.

J Clin Psychiatry. 2017 Jun;78(6):e656-e667. (PMID: 28682528)
Front Oncol. 2022 Jul 07;12:935593. (PMID: 35875146)
Int J Cancer. 2014 Mar 1;134(5):1013-23. (PMID: 23613359)
Int J Mol Sci. 2021 Aug 27;22(17):. (PMID: 34502219)
J Cell Physiol. 2018 Feb;233(2):1370-1383. (PMID: 28518408)
Int J Mol Sci. 2021 Sep 29;22(19):. (PMID: 34638872)
Cancers (Basel). 2021 May 12;13(10):. (PMID: 34065960)
PLoS One. 2017 Feb 3;12(2):e0171582. (PMID: 28158293)
Front Oncol. 2018 Oct 16;8:448. (PMID: 30386738)
Cancers (Basel). 2020 Dec 07;12(12):. (PMID: 33297397)
Int J Mol Sci. 2020 Nov 13;21(22):. (PMID: 33202711)
Annu Rev Pathol. 2014;9:1-25. (PMID: 23937436)
Front Cell Dev Biol. 2015 Mar 05;3:14. (PMID: 25798441)
J Cancer. 2019 Jul 22;10(18):4368-4379. (PMID: 31413757)
Cell Prolif. 2020 Nov;53(11):e12891. (PMID: 33030764)
CA Cancer J Clin. 2020 Jul;70(4):299-312. (PMID: 32478924)
Cancer Cell. 2006 May;9(5):391-403. (PMID: 16697959)
Mol Cell Biol. 2004 Jan;24(2):708-18. (PMID: 14701743)
Cancer Drug Resist. 2021;4:17-43. (PMID: 34337348)
Biol Direct. 2021 Dec 9;16(1):25. (PMID: 34886882)
FASEB J. 1996 Mar;10(4):471-80. (PMID: 8647346)
Mol Oncol. 2022 Jan;16(1):11-41. (PMID: 34036721)
Nat Commun. 2020 Jun 22;11(1):3158. (PMID: 32572033)
Cell Div. 2018 Sep 19;13:7. (PMID: 30250494)
Oncotarget. 2017 Dec 5;8(67):111866-111881. (PMID: 29340097)
Biochem Pharmacol. 2008 Jun 1;75(11):2100-11. (PMID: 18395186)
Ann Hepatol. 2013 Mar-Apr;12(2):183-9. (PMID: 23396728)
Cancer Cell Int. 2018 Dec 04;18:197. (PMID: 30533999)
J Mol Med (Berl). 2020 Apr;98(4):495-512. (PMID: 32219470)
Cancer J. 2021 Sep-Oct 01;27(5):379-385. (PMID: 34570452)
Int J Mol Sci. 2020 Dec 30;22(1):. (PMID: 33396625)
Sci Rep. 2019 Feb 4;9(1):1335. (PMID: 30718768)
Mediators Inflamm. 2015;2015:146282. (PMID: 26491220)
Neurooncol Adv. 2021 Feb 04;3(1):vdab015. (PMID: 33738447)
Cancer Cell Int. 2020 Jun 3;20:213. (PMID: 32518522)
ACS Chem Biol. 2016 Mar 18;11(3):583-97. (PMID: 26540123)
Front Pharmacol. 2021 Nov 25;12:786700. (PMID: 34899350)
PLoS One. 2014 Sep 11;9(9):e107558. (PMID: 25211033)
Annu Rev Genet. 2020 Nov 23;54:25-46. (PMID: 32663049)
FEBS Lett. 2017 Apr;591(8):1114-1125. (PMID: 28337758)
Front Genet. 2015 Mar 20;6:96. (PMID: 25852742)
Cancer Sci. 2009 Dec;100(12):2235-41. (PMID: 19737147)
Asian Pac J Cancer Prev. ;18(1):3-9. (PMID: 28239999)
Oncogene. 2008 Jun 26;27(28):3977-85. (PMID: 18317453)
Brain Res. 2002 Jun 28;942(1-2):46-50. (PMID: 12031851)
Int J Mol Sci. 2020 Jul 27;21(15):. (PMID: 32727112)
Mutat Res. 2013 Aug 30;756(1-2):46-55. (PMID: 23817105)
Cancer Biol Med. 2017 Nov;14(4):348-362. (PMID: 29372101)
Molecules. 2022 Apr 15;27(8):. (PMID: 35458774)
Mol Cell. 2019 May 16;74(4):758-770.e4. (PMID: 30982746)
Cancers (Basel). 2021 Oct 26;13(21):. (PMID: 34771522)
J Cell Physiol. 2019 Aug;234(8):13277-13291. (PMID: 30575033)
Cancers (Basel). 2021 Jun 29;13(13):. (PMID: 34209866)
Cancers (Basel). 2021 Jun 11;13(12):. (PMID: 34208195)
Semin Cancer Biol. 2022 Aug;83:100-120. (PMID: 33370605)
Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1065-70. (PMID: 15650047)
Cell Death Differ. 2008 Jul;15(7):1153-62. (PMID: 18404154)
Neuro Oncol. 2021 Aug 2;23(8):1231-1251. (PMID: 34185076)
Biology (Basel). 2013 Jan 02;2(1):40-63. (PMID: 24832651)
Cell. 2015 Dec 3;163(6):1297-300. (PMID: 26638061)
J Cell Mol Med. 2020 Sep;24(18):10322-10337. (PMID: 32720467)
Int J Mol Sci. 2020 Jul 11;21(14):. (PMID: 32664581)
Front Genet. 2019 Aug 28;10:764. (PMID: 31555321)
Cancers (Basel). 2018 Sep 01;10(9):. (PMID: 30200436)
Nat Commun. 2021 Sep 10;12(1):5380. (PMID: 34508092)
Oncotarget. 2017 Dec 26;9(4):5169-5183. (PMID: 29435170)
Cells. 2022 Jan 25;11(3):. (PMID: 35159219)
Int J Biol Sci. 2010 Dec 06;6(7):784-95. (PMID: 21152119)
Int J Mol Sci. 2022 Jul 12;23(14):. (PMID: 35887021)
Molecules. 2021 Apr 01;26(7):. (PMID: 33915740)
Cell Death Dis. 2020 Oct 13;11(10):850. (PMID: 33051434)
EMBO Rep. 2003 Jul;4(7):671-7. (PMID: 12835754)
Expert Opin Ther Targets. 2020 Jul;24(7):605-614. (PMID: 32394767)
N Engl J Med. 2005 Mar 10;352(10):987-96. (PMID: 15758009)
Front Mol Biosci. 2020 Feb 21;7:24. (PMID: 32154266)
World J Clin Oncol. 2011 Feb 10;2(2):73-9. (PMID: 21603316)

Keywords: DNA damage response; S-Adenosylmethionine; cell cycle arrest and apoptosis; glioblastoma; homologous recombination repair; mitotic catastrophe

7LP2MPO46S (S-Adenosylmethionine)
0 (Antineoplastic Agents)
EC 2.7.11.1 (Aurora Kinase B)
EC 2.7.7.- (Rad51 Recombinase)
EC 2.7.11.1 (AURKB protein, human)

Date Created: 20240427 Date Completed: 20240427 Latest Revision: 20240429

20240429

PMC11052366

10.3390/molecules29081708

38675528