title: Synergistic effect between celecoxib and luteolin is dependent on estrogen receptor in human breast cancer cells.
abstract: The anti-cancer effects of celecoxib and luteolin are well known. Although our previous study demonstrated that the combination of celecoxib and luteolin synergistically inhibits breast tumor growth compared with each of the treatments alone, we did not uncover the molecular mechanisms of these effects. The aims of our present study were to compare the effects of a celecoxib and luteolin combination treatment in four different human breast cell lines and to determine the mechanisms of action in vitro and in vivo. The synergistic effects of a celecoxib and luteolin combination treatment yielded significantly greater cell growth inhibition in all four breast cancer cell lines compared with the single agents alone. In particular, combined celecoxib and luteolin treatment significantly decreased the growth of MDA-MB-231 cancer cells in vivo compared with either agent alone. The celecoxib and luteolin combination treatment induced synergistic effects via Akt inactivation and extracellular signal-regulated kinase (ERK) signaling inhibition in MCF-7 and MCF7/HER18 cells and via Akt inactivation and ERK signaling activation in MDA-MB-231 and SkBr3 cells. These results demonstrate the synergistic anti-tumor effect of the celecoxib and luteolin combination treatment in different four breast cancer cell lines, thus introducing the possibility of this combination as a new treatment modality.
authors: Department of Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, 93 Joongboo-Daero Paldal-gu, Suwon, 442-723, Kyounggi-do, Republic of Korea.
authors: Ye Won
authors: YW
authors: Jeon
authors: Young Ee
authors: YE
authors: Ahn
authors: Won Sang
authors: WS
authors: Chung
authors: Hyun Joo
authors: HJ
authors: Choi
authors: Young Jin
authors: YJ
authors: Suh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects*; D004357:Drug Synergism; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D047311:Luteolin / Q000008:administration & dosage; D020935:MAP Kinase Signaling System / Q000187:drug effects; D061986:MCF-7 Cells; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D011720:Pyrazoles / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D013449:Sulfonamides / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
chemical_list: D000068579:Celecoxib; D047628:Estrogen Receptor alpha; D047311:Luteolin; D051057:Proto-Oncogene Proteins c-akt; D011720:Pyrazoles; D018719:Erb-b2 Receptor Tyrosine Kinases; D013449:Sulfonamides; C506487:ESR1 protein, human; C508053:ERBB2 protein, human