title: COX-2- and endoplasmic reticulum stress-independent induction of ULBP-1 and enhancement of sensitivity to NK cell-mediated cytotoxicity by celecoxib in colon cancer cells.
abstract: In the present study, we investigated whether celecoxib could induce the expression of NKG2D ligands in clonogenic colon cancer cells, and increase their susceptibility to NK cell-mediated cell death. Celecoxib and its non-coxib analog, 2,5-dimethyl celecoxib, induced ULBP-1 and DR5 in both COX-2 negative HCT-15 cells and COX-2 positive HT-29 cells. Celecoxib increased their susceptibility to NK92 cells in both DELFIA assay and soft agar colony forming assay. The inducibility of ULBP-1 and DR5 by celecoxib was not different between CD44- and CD44+ HCT-15 cells, and CD133- and CD133+ HT-29 cells. Celecoxib increased the susceptibility of highly clonogenic CD44+ HCT-15 and CD133+ HT-29 cells to NK92 cells, at least comparable to less clonogenic CD44- HCT-15 and CD133- HT-29 cells, respectively. In addition, celecoxib induced CHOP, and thapsigargin, an inducer of ER (endoplasmic reticulum) stress, induced DR5 but not ULBP1 in HCT-15. Taken together, these findings suggest that celecoxib induces the expression of ULBP-1 as well as DR5 in clonogenic colon cancer cells via COX-2 and ER stress-independent pathways, and increases their susceptibility to NK cells.
authors.affiliation: Department of Biochemistry, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea; MD-PhD program, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: So-Jung
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Ga-Hee
authors.initials: GH
authors.lastname: Ha
authors.affiliation: Department of Biochemistry, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Bae
authors.affiliation: Department of Biochemistry, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Ga Rim
authors.initials: GR
authors.lastname: Kim
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan 619-953, Republic of Korea.
authors.forename: Cheol-Hun
authors.initials: CH
authors.lastname: Son
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan 619-953, Republic of Korea.
authors.forename: You-Soo
authors.initials: YS
authors.lastname: Park
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan 619-953, Republic of Korea.
authors.forename: Kwangmo
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Anatomy, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Sae-Ock
authors.initials: SO
authors.lastname: Oh
authors.affiliation: Department of Biochemistry, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea. Electronic address: ksh7738@pusan.ac.kr.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea. Electronic address: kcdshbw@pusan.ac.kr.
authors.forename: Chi-Dug
authors.initials: CD
authors.lastname: Kang
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000096:biosynthesis; D000068579:Celecoxib; D003110:Colonic Neoplasms / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D006023:Glycoproteins / Q000096:biosynthesis; D019073:HT29 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology*; D010455:Peptides; D011720:Pyrazoles / Q000494:pharmacology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis*; D013449:Sulfonamides / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000096:biosynthesis
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C497483:CD44 protein, human; D052246:Cyclooxygenase 2 Inhibitors; C497249:DDIT3 protein, human; D004791:Enzyme Inhibitors; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D047908:Intracellular Signaling Peptides and Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D011720:Pyrazoles; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D013449:Sulfonamides; C423231:ULBP1 protein, human; D051742:Transcription Factor CHOP; D019284:Thapsigargin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib
keywords: Cancer stem cells; Celecoxib; Colon cancer; NKG2D ligands