Einzeltreffer — DigiBib

ERα and Wnt/β-catenin pathways are critical for the progression of most endometrial cancers. We aimed to investigate the cytotoxic and apoptotic effects of tamoxifen and quinazoline derivative drugs of doxazosin and erlotinib, and their roles in ERα and Wnt/β-catenin signaling pathways in human endometrial cancer RL 95-2 cell. 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay and xCELLigence systems were performed to evaluate cytotoxicity. Furthermore, apoptotic induction was tested by Annexin V analysis. Caspase-3 and -9 activity and changes in the mitochondrial membrane potential were evaluated. The level of reactive oxygen species was measured by incubating with dichlorofluorescein diacetate. Protein ratios of p-ERα/ERα, GSK3β/p-GSK3β, and p-β-catenin/β-catenin and expression levels of ESR1, EGFR, c-Myc genes were evaluated to elucidate mechanisms in signaling pathways. We found that the tested drugs showed cytotoxic and apoptotic effects in the cells. Doxazosin significantly reduced ESR1 expression, slightly reduced the p-β-catenin/β-catenin ratio and c-Myc expression. Erlotinib significantly increased c-Myc expression while significantly decreasing the p-β-catenin/β-catenin and p-ERα/ERα ratio, and ESR1 expression. However, we observed that the cells develop resistance to erlotinib over a certain concentration, suggesting that ERα, ESR1, EGFR, and c-Myc may be a new target for overcoming drug resistance in the treatment of endometrial cancer. We also observed that erlotinib and doxazosin play an important role in the ERα signaling pathway and can act as potent inhibitors of PKA and/or tyrosine kinase in the Wnt/β-catenin signaling pathway in RL 95-2 cell. In conclusion, doxazosin and erlotinib may have a possible therapeutic potential in human endometrial cancer.

Titel:	Doxazosin and erlotinib have anticancer effects in the endometrial cancer cell and important roles in ERα and Wnt/β-catenin signaling pathways.
Autor/in / Beteiligte Person:	Karaca, B ; Bakır, E ; Yerer, MB ; Cumaoğlu, A ; Hamurcu, Z ; Eken, A
Zeitschrift:	Journal of biochemical and molecular toxicology, Jg. 35 (2021-11-01), Heft 11, S. e22905
Veröffentlichung:	New York, NY : Wiley, c1998-, 2021
Medientyp:	academicJournal
ISSN:	1099-0461 (electronic)
DOI:	10.1002/jbt.22905
Schlagwort:	Antineoplastic Agents administration & dosage Doxazosin administration & dosage Endometrial Neoplasms metabolism Endometrial Neoplasms pathology Erlotinib Hydrochloride administration & dosage Estrogen Receptor alpha metabolism Female Humans beta Catenin metabolism Antineoplastic Agents therapeutic use Doxazosin therapeutic use Endometrial Neoplasms drug therapy Erlotinib Hydrochloride therapeutic use Estrogen Receptor alpha drug effects Wnt Signaling Pathway drug effects beta Catenin drug effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [J Biochem Mol Toxicol] 2021 Nov; Vol. 35 (11), pp. e22905. <i>Date of Electronic Publication: </i>2021 Aug 30. MeSH Terms: Antineoplastic Agents / therapeutic use ; Doxazosin / therapeutic use ; Endometrial Neoplasms / drug therapy ; Erlotinib Hydrochloride / therapeutic use ; Estrogen Receptor alpha / drug effects ; Wnt Signaling Pathway / drug effects ; beta Catenin / *drug effects ; Antineoplastic Agents / administration & dosage ; Doxazosin / administration & dosage ; Endometrial Neoplasms / metabolism ; Endometrial Neoplasms / pathology ; Erlotinib Hydrochloride / administration & dosage ; Estrogen Receptor alpha / metabolism ; Female ; Humans ; beta Catenin / metabolism References: A. Markowska, M. Pawałowska, J. Lubin, J. Markowska, Contemp. Oncol. 2014, 18(3), 143. ; S. Wedren, L. Lovmar, K. Humphreys, C. Magnusson, H. Melhus, A.-C. Syvanen, A. Kindmark, U. Landegren, M. L. Fermer, F. Stiger, I. Persson, J. A. Baron, E. Weiderpass, BMC Cancer 2008, 8, 322. ; A. C. Rodriguez, Z. Blanchard, K. A. Maurer, J. Gertz, Horm. Cancer 2019, 10(2-3), 51. ; F. Shan, Z. Shao, S. Jiang, Z. Cheng, Cancer Med. 2016, 5(11), 3166. ; S. Shang, F. Hua, Z.-W. Hu, Oncotarget 2017, 8(20), 33972. ; S. Hino, C. Tanji, K. I. Nakayama, A. Kikuchi, Mol. Cell. Biol. 2005, 25(20), 9063. ; S. Taurin, N. Sandbo, Y. Qin, D. Browning, N. O. Dulin, J. Biol. Chem. 2006, 281(15), 9971. ; C. Wang, J. A. Mayer, A. Mazumdar, K. Fertuck, H. Kim, M. Brown, P. H. Brown, Mol. Endocrinol. 2011, 25(9), 1527. ; G. Marzaro, A. Guiotto, A. Chilin, Expert Opin. Ther. Patents 2012, 22(3), 223. ; C. Cal, R. Uslu, G. Gunaydın, C. Ozyurt, S. B. Omay, BJU Int. 2000, 85, 672. ; H. Hui, M. A. Fernando, A. P. Heaney, Eur. J. Cancer 2008, 44, 160. ; F. Z. El Sharkawi, H. A. El Shemy, H. M. Khaled, Asian Pac. J. Cancer Prev. 2014, 15(1), 199. ; B. Pagan, A. A. Isidro, M. L. Cruz, Y. Ren, D. Coppola, J. Wu, C. B. Appleyard, World J. Gastroenterol. 2011, 17(44), 4858. ; Y. Shao, Y. Yu, R. Zong, L. Quyang, H. He, Q. Zhou, C. Pei, Biomed. Pharmacother. 2017, 85, 479. ; Y. M. Shah, M. Al-Dhaheri, Y. Dong, C. Ip, F. E. Jones, B. G. Rowan, Mol. Cancer Ther. 2005, 4(8), 1239. ; A.-C. Huang, T.-P. Lin, Y.-S. Weng, Y.-T. Ho, H.-J. Lin, L.-J. Huang, S.-C. Kuo, J.-G. Chung, Anticancer Res. 2007, 27, 2505. ; T.-E. Wang, Y.-K. Wang, J. Jin, B.-L. Xu, X.-G. Chen, Int. J. Oncol. 2014, 45, 771. ; B. Karaca, E. Bakır, A. Eken, J. Health Sci. 2019, 28, 47. ; A. K. Karaboğa-Arslan, M. B. Yerer, Nutrients 2018, 10(672), 2. ; H. Wang, J. A. Joseph, Free Radical Biol. Med. 1999, 27(5-6), 612. ; Z. D. Ozdal, E. Sahmetlioğlu, I. Narin, A. Cumaoğlu, 3 Biotech. 2019, 9, 212. ; L. Petinari, L. Konecny-Kohn, J. E. Carvalho, S. Candelaria-Genari, Cell Biol. Int. 2004, 28, 531. ; M. Glaeser, D. Niederacher, S. Djahansouzi, B. Hanstein, R. Dittrich, M. W. Beckmann, P. A. Fasching, S. Ackermann, Anticancer Res. 2006, 26, 735. ; C. M. Benning, N. Kyprianou, Cancer Res. 2002, 62, 597. ; N. Han, Q. Zhou, Q. Huang, K. Liu, Biomed. Pharmacother. 2017, 89, 827. ; L. A. Cantrell, C. Zhou, A. Mendivil, K. M. Malloy, P. A. Gehrig, V. L. Bae-Jump, Gynecol. Oncol. 2010, 116, 92. ; H. Huang, Y. Shi, H. He, Y. Wang, T. Chen, L. Yang, T. Yang, J. Chen, J. Cao, W. Yao, G. Liu, Cell. Physiol. Biochem. 2017, 42, 889. ; Y. Gorzalczany, Y. Gilad, D. Amihai, I. Hammel, R. Sagi-Eisenberg, O. Merimsky, Cancer Lett. 2011, 310, 207. ; C. M. P. Cardoso, L. M. Almeida, J. B. A. Custodio, Mitochondrion 2002, 1, 485. ; S. J. Kim, H. S. Kim, Y. R. Seo, Oxid. Med. Cell. Longevity 2019, 2019, 12. ; A. Lebeau, T. J. Grob, F. Holst, N. Seyedi-Fazlollahi, H. Moch, L. Terracciano, A. Turzynski, J. Pathol. 2008, 216, 151. ; C. C. Tu, V. B. Kumar, C. H. Day, W. W. Kuo, S. P. Yeh, R. J. Chen, C. R. Liao, H. Y. Chen, F. J. Tsai, W. J. Wu, C. Y. Huang, J. Mol. Endocrinol. 2013, 51, 203. ; J. G. Moggs, T. C. Murphy, F. L. Lim, D. J. Moore, R. Stuckey, K. Antrobus, I. Kimber, G. Orphanides, J. Mol. Endocrinol. 2005, 34(2), 535. ; B. B. Tu, S. L. Lin, L. Y. Yan, Z. Y. Wang, Q. Y. Sun, J. Qiao, Am. J. Obstet. Gynecol. 2011, 205, 227.e2. ; G. Li, J. Zhang, K. Jin, K. He, Y. Zheng, X. Xua, H. Wang, H. Wang, Z. Li, X. Yu, X. Teng, J. Cao, L. Teng, Mol. Oncol. 2013, 7, 611. ; L. Liu, J. Zhang, X. Yang, C. Fang, H. Xu, X. Xi, PLoS One 2015, 10(9), e0138515. ; S. L. Lin, L. Y. Yan, X. T. Zhang, J. Yuan, M. Li, J. Qiao, Z. Y. Wang, Q. Y. Sun, PLoS One 2010, 5(2), e9013. ; F. Mitsui, Y. Dobashi, I. Imoto, J. Inazawa, K. Kono, H. Fujii, A. Ooi, Mod. Pathol. 2007, 20, 622. ; M. S. Park, B. R. Kim, S. Kang, D. Y. Kim, S. B. Rho, Genes Cancer 2014, 5(11-12), 470. ; N. Steen, L. Potze, E. Giovannetti, A. Cavazzoni, R. Ruijtenbeek, C. Rolfo, P. Pauwels, G. J. Peters, Am. J. Cancer Res. 2017, 7(4), 816. ; J. Gauduchon, F. Gouilleux, S. Maillard, V. Marsaud, J. M. Renoir, B. Sola, Clin. Cancer Res. 2005, 11, 2345. ; J. Wang, X. Wang, W. Gong, B. Mi, S. Liu, B. Jiang, J. Histochem. Cytochem. 2009, 57(4), 363. ; N. T. Solberg, J. Waaler, K. Lund, L. Mygland, P. A. Olsen, S. Krauss, Mol. Cancer Res. 2017, 16(3), 543. ; C. Li, C. Zhou, S. Wang, Y. Feng, W. Lin, S. Lin, Y. Wang, H. Huang, P. Liu, Y.-G. Mu, X. Shen, PLoS One 2011, 6, e27053. ; C.-H. Lee, H.-W. Hung, P.-H. Hung, Y.-S. Shieh, Mol. Cancer 2010, 9, 64. Grant Information: TDK-2017-7874 Erciyes Üniversitesi; TSA-2018-7896 Erciyes Üniversitesi Contributed Indexing: Keywords: Wnt/β-catenin; apoptosis; cytotoxicity; doxazosin; erlotinib Substance Nomenclature: 0 (Antineoplastic Agents) ; 0 (CTNNB1 protein, human) ; 0 (Estrogen Receptor alpha) ; 0 (beta Catenin) ; DA87705X9K (Erlotinib Hydrochloride) ; NW1291F1W8 (Doxazosin) Entry Date(s): Date Created: 20210831 Date Completed: 20220221 Latest Revision: 20220221 Update Code: 20240513

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.

Doxazosin and erlotinib have anticancer effects in the endometrial cancer cell and important roles in ERα and Wnt/β-catenin signaling pathways.