title: Myeloid zinc finger 1 mediates sulindac sulfide-induced upregulation of death receptor 5 of human colon cancer cells.
abstract: A combined therapy of sulindac sulfide and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising strategy for the treatment of cancer. Sulindac sulfide had been shown to induce the expression of death receptor 5 (DR5), a receptor for TRAIL, and sensitize cancer cells to TRAIL-induced apoptosis; however, the molecular mechanism underlying the upregulation of DR5 has not yet been elucidated. We demonstrate here that myeloid zinc finger 1 (MZF1) mediates the induction of DR5 by sulindac sulfide. Sulindac sulfide induced the expression of DR5 at the protein and mRNA levels in colon cancer SW480 cells. Furthermore, sulindac sulfide increased DR5 promoter activity. We showed that sulindac sulfide stimulated DR5 promoter activity via the -301 to -253 region. This region contained a putative MZF1-binding site. Site-directed mutations in the site abrogated the enhancement in DR5 promoter activity by sulindac sulfide. MZF1 directly bound to the putative MZF1-binding site of the DR5 promoter and the binding was increased by sulindac sulfide. The expression of MZF1 was also increased by sulindac sulfide, and MZF1 siRNA attenuated the upregulation of DR5 by sulindac sulfide. These results indicate that sulindac sulfide induces the expression of DR5 by up-regulating MZF1.
authors.affiliation: 1] Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan [2].
authors.forename: Mano
authors.initials: M
authors.lastname: Horinaka
authors.affiliation: 1] Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan [2].
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tomosugi
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sowa
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakai
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D013467:Sulindac / Q000031:analogs & derivatives* / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D051741:Kruppel-Like Transcription Factors; C085969:MZF1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D013467:Sulindac; C025462:sulindac sulfide
references.citation: Nat Cell Biol. 2001 Apr;3(4):409-16
references.pmid: 11283615
references.citation: Lancet. 2011 Jan 1;377(9759):31-41
references.pmid: 21144578
references.citation: J Biol Chem. 1996 May 31;271(22):12687-90
references.pmid: 8663110
references.citation: Cancer Res. 2005 Jul 1;65(13):5662-7
references.pmid: 15994939
references.citation: EMBO J. 1997 Sep 1;16(17):5386-97
references.pmid: 9311998
references.citation: Nat Med. 1999 Feb;5(2):157-63
references.pmid: 9930862
references.citation: Oncogene. 2000 Mar 30;19(14):1735-43
references.pmid: 10777207
references.citation: Nat Rev Cancer. 2008 Oct;8(10):782-98
references.pmid: 18813321
references.citation: Genes Dev. 2001 Jul 1;15(13):1625-30
references.pmid: 11445537
references.citation: Cancer Gene Ther. 2005 Mar;12(3):228-37
references.pmid: 15550937
references.citation: Cancer Res. 1995 Aug 15;55(16):3610-4
references.pmid: 7627970
references.citation: Apoptosis. 2009 Nov;14(11):1341-51
references.pmid: 19757064
references.citation: FEBS Lett. 2010 Feb 5;584(3):577-82
references.pmid: 19995562
references.citation: Environ Health Prev Med. 2010 Jul;15(4):203-10
references.pmid: 21432546
references.citation: J Biol Chem. 1997 Oct 10;272(41):25417-20
references.pmid: 9325248
references.citation: FEBS Lett. 2001 Nov 2;507(3):381-5
references.pmid: 11696376
references.citation: Cell. 1997 Feb 7;88(3):323-31
references.pmid: 9039259
references.citation: Mol Cell Biol. 2005 Jul;25(13):5404-16
references.pmid: 15964798
references.citation: Oncogene. 2002 Sep 5;21(39):6032-40
references.pmid: 12203115
references.citation: Curr Biol. 1997 Sep 1;7(9):693-6
references.pmid: 9285725
references.citation: J Biol Chem. 2004 Oct 29;279(44):45495-502
references.pmid: 15322075
references.citation: Science. 1997 Aug 8;277(5327):815-8
references.pmid: 9242610
references.citation: Mol Cancer Ther. 2006 Apr;5(4):945-51
references.pmid: 16648565
references.citation: Cell Death Differ. 2003 Jan;10(1):66-75
references.pmid: 12655296
references.citation: Cancer Cell. 2004 May;5(5):501-12
references.pmid: 15144957
references.citation: N Engl J Med. 2007 May 24;356(21):2131-42
references.pmid: 17522398
references.citation: Vitam Horm. 2004;67:35-49
references.pmid: 15110170
references.citation: J Immunol. 2005 Nov 1;175(9):5586-90
references.pmid: 16237043
references.citation: J Clin Invest. 1999 Jul;104(2):155-62
references.pmid: 10411544
references.citation: Science. 1997 Aug 8;277(5327):818-21
references.pmid: 9242611
references.citation: Int J Oncol. 2013 Mar;42(3):903-11
references.pmid: 23354042
references.citation: Oncogene. 2004 Aug 19;23(37):6261-71
references.pmid: 15208660
references.citation: Cancer Sci. 2012 Feb;103(2):282-7
references.pmid: 22077238
references.citation: J Immunol. 2007 Oct 15;179(8):5441-53
references.pmid: 17911631
references.citation: Cancer Res. 1994 Sep 15;54(18):4855-78
references.pmid: 8069852
references.citation: Lancet. 2012 Apr 28;379(9826):1591-601
references.pmid: 22440947
references.citation: Carcinogenesis. 2004 Oct;25(10):1853-8
references.pmid: 15180942
references.citation: Cancer Res. 2005 Jul 15;65(14):6364-70
references.pmid: 16024639
references.citation: Lancet. 2003 Jul 19;362(9379):230-2
references.pmid: 12885487
references.citation: Nat Genet. 1997 Oct;17(2):141-3
references.pmid: 9326928
references.citation: Cancer Res. 2001 Sep 15;61(18):6918-24
references.pmid: 11559570
references.citation: Mol Cancer Ther. 2009 Dec;8(12):3331-40
references.pmid: 19996273
references.citation: J Exp Med. 2002 Jan 21;195(2):161-9
references.pmid: 11805143
references.citation: Cancer Res. 2008 Nov 1;68(21):8918-27
references.pmid: 18974136
references.citation: Nat Med. 2001 Apr;7(4):383-5
references.pmid: 11283636
references.citation: Immunity. 1995 Dec;3(6):673-82
references.pmid: 8777713
references.citation: Neoplasia. 2001 Nov-Dec;3(6):535-46
references.pmid: 11774036
references.citation: J Clin Oncol. 2008 Jul 20;26(21):3621-30
references.pmid: 18640940