Einzeltreffer — DigiBib

Resistance to anticancer drugs is a problem in the treatment of pancreatic ductal carcinoma (PDAC) and overcoming it is an important issue. Recently, it has been reported that statins induce apoptosis in cancer cells but the mechanism has not been completely elucidated. We investigated the antitumor mechanisms of statins against PDAC and their impact on resistance to gemcitabine (GEM). Lovastatin (LOVA) increased mitochondrial oxidative stress in PDAC cells, leading to apoptosis. LOVA reduced lipid rafts in the plasma membrane and mitochondria, suppressed the activation of epithelial growth factor receptor (EGFR) and AKT in plasma membrane rafts, and reduced B-cell lymphoma 2 (BCL2)-Bcl-2-associated X protein (BAX) binding and the translocation of F1F0 ATPase in mitochondrial rafts. In the three GEM-resistant cell lines derived from MIA and PANC1, the lipid rafts in the cell membrane and the mitochondria were increased to activate EGFR and AKT and to increase BCL2-BAX binding, which suppressed apoptosis. LOVA abrogated these anti-apoptotic effects by reducing the rafts in the resistant cells. By treating the resistant cells with LOVA, GEM sensitivity improved to the level of the parental cells. Therefore, cholesterol rafts contribute to drug resistance in PDAC. Further clinical research is warranted on overcoming anticancer drug resistance by statin-mediated intracellular cholesterol regulation.

Titel:	Lovastatin Treatment Inducing Apoptosis in Human Pancreatic Cancer Cells by Inhibiting Cholesterol Rafts in Plasma Membrane and Mitochondria.
Autor/in / Beteiligte Person:	Gyoten, M ; Luo, Y ; Fujiwara-Tani, R ; Mori, S ; Ogata, R ; Kishi, S ; Kuniyasu, H
Link:	Zum Volltext
Zeitschrift:	International journal of molecular sciences, Jg. 24 (2023-11-27), Heft 23
Veröffentlichung:	Basel, Switzerland : MDPI, [2000-, 2023
Medientyp:	academicJournal
ISSN:	1422-0067 (electronic)
DOI:	10.3390/ijms242316814
Schlagwort:	Humans bcl-2-Associated X Protein metabolism Lovastatin pharmacology Proto-Oncogene Proteins c-akt metabolism Apoptosis Cell Membrane metabolism Gemcitabine Membrane Microdomains metabolism ErbB Receptors metabolism Mitochondria metabolism Cholesterol metabolism Cell Line, Tumor Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology Antineoplastic Agents pharmacology Antineoplastic Agents metabolism Pancreatic Neoplasms drug therapy Pancreatic Neoplasms metabolism Carcinoma, Pancreatic Ductal metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Int J Mol Sci] 2023 Nov 27; Vol. 24 (23). <i>Date of Electronic Publication: </i>2023 Nov 27. MeSH Terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors* / pharmacology ; Antineoplastic Agents* / pharmacology ; Antineoplastic Agents* / metabolism ; Pancreatic Neoplasms* / drug therapy ; Pancreatic Neoplasms* / metabolism ; Carcinoma, Pancreatic Ductal* / metabolism ; Humans ; bcl-2-Associated X Protein / metabolism ; Lovastatin / pharmacology ; Proto-Oncogene Proteins c-akt / metabolism ; Apoptosis ; Cell Membrane / metabolism ; Gemcitabine ; Membrane Microdomains / metabolism ; ErbB Receptors / metabolism ; Mitochondria / metabolism ; Cholesterol / metabolism ; Cell Line, Tumor References: Int J Mol Sci. 2020 May 28;21(11):. (PMID: 32481659) ; Biochim Biophys Acta. 2014 Jan;1841(1):190-203. (PMID: 24120917) ; Front Oncol. 2013 Feb 19;3:25. (PMID: 23424713) ; Mol Cancer. 2017 Feb 28;16(1):52. (PMID: 28245823) ; J Pathol. 2002 Feb;196(2):163-70. (PMID: 11793367) ; Pharmaceutics. 2021 May 20;13(5):. (PMID: 34065546) ; J Cell Mol Med. 2001 Oct-Dec;5(4):378-87. (PMID: 12067471) ; Oncol Lett. 2018 Apr;15(4):4423-4426. (PMID: 29556289) ; JAMA. 2021 Sep 7;326(9):851-862. (PMID: 34547082) ; Int J Mol Sci. 2021 Mar 06;22(5):. (PMID: 33800828) ; Toxicol Appl Pharmacol. 2012 Mar 15;259(3):311-9. (PMID: 22289360) ; Anticancer Agents Med Chem. 2014 Jun;14(5):706-12. (PMID: 24295174) ; Curr Med Chem. 2018;25(22):2595-2607. (PMID: 28403788) ; Biochim Biophys Acta. 1975 Nov 17;413(1):116-34. (PMID: 172147) ; Methods Mol Biol. 2021;2187:147-186. (PMID: 32770506) ; Mol Cell Endocrinol. 1985 May;40(2-3):233-43. (PMID: 4007257) ; Methods Mol Biol. 2015;1232:91-102. (PMID: 25331130) ; Int J Mol Sci. 2022 Jul 15;23(14):. (PMID: 35887170) ; Int J Mol Sci. 2023 Apr 19;24(8):. (PMID: 37108667) ; J Hematol Oncol. 2021 Jan 13;14(1):14. (PMID: 33436044) ; Nat Rev Dis Primers. 2016 Apr 21;2:16022. (PMID: 27158978) ; Apoptosis. 2015 May;20(5):621-34. (PMID: 25652700) ; Mol Endocrinol. 2015 Apr;29(4):490-501. (PMID: 25730708) ; Pancreas. 2020 Mar;49(3):326-335. (PMID: 32132516) ; Annu Rev Pathol. 2023 Jan 24;18:123-148. (PMID: 36130070) ; J Exp Clin Cancer Res. 2022 Mar 8;41(1):88. (PMID: 35260193) ; Ann Med. 2022 Dec;54(1):1287-1296. (PMID: 35533049) ; Pharmacol Res. 2020 Oct;160:105081. (PMID: 32679179) ; Prim Care. 2013 Mar;40(1):195-211. (PMID: 23402469) ; J Exp Clin Cancer Res. 2021 Jul 24;40(1):241. (PMID: 34303383) ; Int J Mol Sci. 2019 Sep 11;20(18):. (PMID: 31514451) ; FEBS J. 2018 Feb;285(3):416-431. (PMID: 28755482) ; Cancer Prev Res (Phila). 2021 Sep;14(9):863-872. (PMID: 34244151) ; Front Genet. 2021 Sep 16;12:724149. (PMID: 34603386) ; Drug Resist Updat. 2015 Nov;23:55-68. (PMID: 26690340) ; Chem Biol Interact. 2022 Sep 25;365:110106. (PMID: 35985521) ; Therapie. 1992 Mar-Apr;47(2):161-4. (PMID: 1412144) ; Int J Oncol. 1998 Mar;12(3):717-23. (PMID: 9472115) ; Medicine (Baltimore). 2016 May;95(19):e3607. (PMID: 27175667) ; Antioxid Redox Signal. 2014 Jul 1;21(1):66-85. (PMID: 24483238) Grant Information: 19K16564 Ministry of Education, Culture, Sports, Science and Technology; 20K21659 Ministry of Education, Culture, Sports, Science and Technology; 23K16621 Ministry of Education, Culture, Sports, Science and Technology; 23K19900 Ministry of Education, Culture, Sports, Science and Technology Contributed Indexing: Keywords: apoptosis; drug resistance; mitochondrial raft; pancreas cancer; statin Substance Nomenclature: 0 (bcl-2-Associated X Protein) ; 9LHU78OQFD (Lovastatin) ; EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) ; 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) ; 0 (Antineoplastic Agents) ; 0 (Gemcitabine) ; EC 2.7.10.1 (ErbB Receptors) ; 97C5T2UQ7J (Cholesterol) Entry Date(s): Date Created: 20231209 Date Completed: 20231216 Latest Revision: 20231216 Update Code: 20231218 PubMed Central ID: PMC10706654

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

BibTeX Citavi, JabRef, u.a.
(Literaturverwaltung)

PDF kein Volltext!
(Merkzettel, Notizen)

RIS Endnote, Citavi u.a.
(Literaturverwaltung)

MODS
(XML zur Weiterverarbeitung)

oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

Gewünschter Zitations-Stil:

oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

Lovastatin Treatment Inducing Apoptosis in Human Pancreatic Cancer Cells by Inhibiting Cholesterol Rafts in Plasma Membrane and Mitochondria.