PMID- 25102912 OWN - NLM STAT- MEDLINE DCOM- 20151117 LR - 20211021 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 4 DP - 2014 Aug 8 TI - Myeloid zinc finger 1 mediates sulindac sulfide-induced upregulation of death receptor 5 of human colon cancer cells. PG - 6000 LID - 10.1038/srep06000 [doi] LID - 6000 AB - 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. FAU - Horinaka, Mano AU - Horinaka M AD - 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]. FAU - Yoshida, Tatsushi AU - Yoshida T AD - 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]. FAU - Tomosugi, Mitsuhiro AU - Tomosugi M AD - Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. FAU - Yasuda, Shusuke AU - Yasuda S AD - Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. FAU - Sowa, Yoshihiro AU - Sowa Y AD - Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. FAU - Sakai, Toshiyuki AU - Sakai T AD - Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140808 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Antineoplastic Agents) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (MZF1 protein, human) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand) RN - 0 (TNF-Related Apoptosis-Inducing Ligand) RN - 184SNS8VUH (Sulindac) RN - 6UVA8S2DEY (sulindac sulfide) SB - IM MH - Antineoplastic Agents/*pharmacology MH - Apoptosis/drug effects MH - Binding Sites MH - Cell Line, Tumor MH - Colonic Neoplasms/metabolism/pathology MH - DNA Fragmentation/drug effects MH - HCT116 Cells MH - Humans MH - Kruppel-Like Transcription Factors/antagonists & inhibitors/genetics/*metabolism MH - Mutagenesis, Site-Directed MH - Promoter Regions, Genetic MH - RNA Interference MH - RNA, Messenger/metabolism MH - RNA, Small Interfering/metabolism MH - Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/*metabolism MH - Sulindac/*analogs & derivatives/pharmacology MH - TNF-Related Apoptosis-Inducing Ligand/pharmacology MH - Up-Regulation/*drug effects PMC - PMC4126006 EDAT- 2014/08/12 06:00 MHDA- 2015/11/18 06:00 PMCR- 2014/08/08 CRDT- 2014/08/09 06:00 PHST- 2014/02/26 00:00 [received] PHST- 2014/07/22 00:00 [accepted] PHST- 2014/08/09 06:00 [entrez] PHST- 2014/08/12 06:00 [pubmed] PHST- 2015/11/18 06:00 [medline] PHST- 2014/08/08 00:00 [pmc-release] AID - srep06000 [pii] AID - 10.1038/srep06000 [doi] PST - epublish SO - Sci Rep. 2014 Aug 8;4:6000. doi: 10.1038/srep06000.