title: HSP90 Inhibition Suppresses PGE2 Production via Modulating COX-2 and 15-PGDH Expression in HT-29 Colorectal Cancer Cells.
abstract: The existence of multiple-interactive roles between several signaling pathways in tumorigenesis shows the significance of pharmacological factors like heat shock protein 90 (HSP90) inhibitors which control several signaling pathways simultaneously. HSP90 as a molecular chaperone supports the active conformational structure and function of several oncogenic signal proteins, termed "client" proteins, some of them act as a link between cancer and inflammation. Prostaglandin E2 (PGE2) is one of the major mediators of inflammation in colorectal cancer development and progress. However, the relationship between chaperone activity of HSP90 and PGE2 levels remains unclear. We evaluated the inhibitory effects of 17-demethoxy-17-allylamino geldanamycin (1 7-AAG), an HSP90 inhibitor, on PGE2 levels in HT-29 colorectal cancer cells. For the first time, we showed inhibitory effects of 17-AAG, on PGE2 levels in HT-29 colorectal cancer cells. 17-AAG inhibited PMA-induced cyclooxygenase-2 (COX-2) mRNA expression and protein level. We showed 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression induced by 17-AAG treatment at both mRNA and protein levels. In conclusion, we found that inhibitory effects of 17-AAG on PGE2 levels in HT-29 colorectal cancer cells were mediated through modulating COX-2 and 15-PGDH expression.
authors.affiliation: Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.|Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Mohammadi
authors.affiliation: Research Department of Biotechnology, Institute of Sciences and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.
authors.forename: M M
authors.initials: MM
authors.lastname: Yaghoobi
authors.affiliation: Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Gholamhoseinian Najar
authors.affiliation: Department of Oncology and Hematology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: B
authors.initials: B
authors.lastname: Kalantari-Khandani
authors.affiliation: Modeling in Health Rersearch Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Sharifi
authors.affiliation: Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran. moh.saravani@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Saravani
mesh_terms: D016227:Benzoquinones / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D019073:HT29 Cells; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D015398:Signal Transduction
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D012333:RNA, Messenger; C112765:tanespimycin; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: 15-PGDH; COX-2; HSP90; PGE2; colorectal cancer