title: Temozolomide may induce cell cycle arrest by interacting with URG4/URGCP in SH-SY5Y neuroblastoma cells.
abstract: Temozolomide (TMZ) is an alkylating drug used usually in glioma treatment by inducing the apoptosis in glioma cell. The aim of the study is to investigate the anticancer mechanism of TMZ in SH-SY5Y human neuroblastoma cell line. Cytotoxic effects of TMZ were determined by using XTT assay. IC50 doses in the SH-SY5Y were detected as 5 mM. Expression profiles of novel genes URG4/URGCP, CCND1, CCND2, CDK4, and BCL2 were determined by real-time PCR. The apoptotic effects of TMZ were evaluated with TUNEL method. Furthermore, effects of TMZ on colony formation and invasion were investigated in this study. It was observed that TMZ in SH-SY5Y cell line caused a significant decrease in the gene expressions of URG4/URGCP, CCND1, CCND2, CDK4, and BCL2. According to TUNEL assay results, TMZ markedly induced apoptosis in SH-SY5Y cell line. It was found that TMZ in SH-SY5Y cell line suppressed invasion and colony formation using matrigel invasion chamber and colony formation assay, respectively. To conclude, it is thought that TMZ demonstrates anticarcinogenesis activity by affecting cell cycle arrest, apoptosis, invasion, and colony formation on SH-SY5Y cells. TMZ may be an effective agent for treatment of neuroblastoma as a single or in combination with other drugs.
authors.affiliation: Department of Neurosurgery, Pamukkale University School of Medicine, Denizli, Turkey.
authors.forename: Veli
authors.initials: V
authors.lastname: Çıtışlı
authors.affiliation: Department of Medical Biology, Pamukkale University School of Medicine, Denizli, Turkey. yavuzdodurga@gmail.com.
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Dodurga
authors.affiliation: Department of Medical Biology, Pamukkale University School of Medicine, Denizli, Turkey.
authors.forename: Canan
authors.initials: C
authors.lastname: Eroğlu
authors.affiliation: Department of Medical Biology, Pamukkale University School of Medicine, Denizli, Turkey.
authors.forename: Mücahit
authors.initials: M
authors.lastname: Seçme
authors.affiliation: Department of Medical Biology, Ege University School of Medicine, Izmir, Turkey.
authors.forename: Çığır Biray
authors.initials: ÇB
authors.lastname: Avcı
authors.affiliation: Department of Forensic Medicine, Ankara University School of Medicine, Ankara, Turkey.
authors.forename: N Lale
authors.initials: NL
authors.lastname: Şatıroğlu-Tufan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000077204:Temozolomide
chemical_list: D009363:Neoplasm Proteins; C470990:URGCP protein, human; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Neuroblastoma; SH-SY5Y cell; Temozolamide; URG4/URGCP
references.citation: Science. 1997 Feb 21;275(5303):1129-32
references.pmid: 9027314
references.citation: Expert Rev Anticancer Ther. 2011 Dec;11(12):1935-44
references.pmid: 22117160
references.citation: Oncol Rep. 2011 Sep;26(3):543-50
references.pmid: 21617871
references.citation: Cell Death Differ. 2004 Apr;11(4):448-57
references.pmid: 14713959
references.citation: Breast Cancer Res. 2013 Jan 21;15(1):R5
references.pmid: 23336272
references.citation: J Biol Chem. 2003 Feb 14;278(7):5292-9
references.pmid: 12471035
references.citation: BMC Cancer. 2014 Jan 13;14 :17
references.pmid: 24418474
references.citation: Oncol Lett. 2011 Nov;2(6):1165-1170
references.pmid: 22848283
references.citation: Br J Cancer. 2003 Feb 10;88(3):463-9
references.pmid: 12569392
references.citation: Neuro Oncol. 2011 Apr;13(4):384-92
references.pmid: 21317208
references.citation: Neuro Oncol. 2000 Oct;2(4):221-8
references.pmid: 11265231
references.citation: Nat Rev Cancer. 2011 Jul 07;11(8):558-72
references.pmid: 21734724
references.citation: Neoplasia. 2002 Jul-Aug;4(4):355-68
references.pmid: 12082552
references.citation: Pediatr Blood Cancer. 2006 Jul;47(1):30-6
references.pmid: 16047361
references.citation: Br J Cancer. 1998 Sep;78(5):652-61
references.pmid: 9744506
references.citation: Genet Mol Res. 2010 Aug 10;9(3):1557-67
references.pmid: 20714998
references.citation: Clin Cancer Res. 2009 Feb 15;15(4):1241-9
references.pmid: 19174487
references.citation: Chin Med J (Engl). 2009 Jun 5;122(11):1260-6
references.pmid: 19567134
references.citation: Lancet. 2007 Jun 23;369(9579):2106-20
references.pmid: 17586306
references.citation: Clin Cancer Res. 2000 Mar;6(3):998-1007
references.pmid: 10741727
references.citation: Curr Top Dev Biol. 2011;94:77-127
references.pmid: 21295685
references.citation: Clin Cancer Res. 2013 Nov 15;19(22):6173-82
references.pmid: 24045179
references.citation: Pathology. 2009 Feb;41(2):149-54
references.pmid: 18972316
references.citation: Mol Biol Rep. 2014 Jul;41(7):4595-9
references.pmid: 24652203
references.citation: J Clin Oncol. 2003 Feb 15;21(4):646-51
references.pmid: 12586801
references.citation: Cancer Res. 2007 Oct 15;67(20):9809-16
references.pmid: 17942911
references.citation: Cancer Res. 2008 Apr 15;68(8):2599-609
references.pmid: 18413728
references.citation: PLoS One. 2014 Aug 11;9(8):e104538
references.pmid: 25111384
references.citation: J Clin Oncol. 2002 Mar 1;20(5):1375-82
references.pmid: 11870182
references.citation: Neoplasia. 2006 Dec;8(12):995-1002
references.pmid: 17217616
references.citation: Nat Rev Cancer. 2003 Mar;3(3):203-16
references.pmid: 12612655
references.citation: J Clin Oncol. 2006 Nov 20;24(33):5259-64
references.pmid: 17114659
references.citation: Cell Cycle. 2010 Feb 15;9(4):689-99
references.pmid: 20107323
references.citation: J Clin Oncol. 2000 Apr;18(7):1481-91
references.pmid: 10735896
references.citation: J Neurooncol. 2012 Apr;107(2):359-64
references.pmid: 22045118
references.citation: DNA Repair (Amst). 2007 Aug 1;6(8):1079-99
references.pmid: 17485253
references.citation: Int J Cancer. 2013 Oct 15;133(8):1982-93
references.pmid: 23564480
references.citation: Biochem Pharmacol. 1987 Feb 15;36(4):457-62
references.pmid: 3470008
references.citation: Clin Cancer Res. 2008 Feb 1;14 (3):931-8
references.pmid: 18245557
references.citation: Eur J Cancer. 2000 Sep;36(14 ):1788-95
references.pmid: 10974627
references.citation: J Int Med Res. 2014 Feb;42(1):164-72
references.pmid: 24326954
references.citation: Expert Rev Anticancer Ther. 2006 Aug;6(8):1187-204
references.pmid: 16925485
references.citation: Mol Biol Rep. 2013 Apr;40(4):3043-8
references.pmid: 23266667
references.citation: Biomed Res Int. 2014;2014:747415
references.pmid: 25295271
references.citation: Eur J Cancer. 2014 Jan;50(1):170-7
references.pmid: 24021349