title: 4-hexylresorcinol inhibits NF-κB phosphorylation and has a synergistic             effect with cisplatin in KB cells.
abstract: Cisplatin is a representative anti-cancer drug and 4-hexylresorcinol (4-HR)             is known as an antiparasitic and antiseptic agent. The aims of this study were             to evaluate the effect of 4-HR on the activation of nuclear factor-κB (NF-κB)             in cell cultures, to evaluate the antitumor effect of 4-HR plus cisplatin combination             therapy in a xenograft model, and to evaluate transglutaminase-2 (TG-2) and phosphorylated             NF-κB (pNF-κB) expression in the xenograft model. To determine the effect of 4-HR             on NF-κB phosphorylation, co-immunoprecipitation and Western blot analysis were             done in KB cells. To examine the in vivo effect of the cisplatin plus 4-HR combination             therapy, KB cells were grafted into nude mice. Drugs were injected into the peritoneal             cavity daily. Tumor size, body weight, and duration of survival were checked daily.             Specimens from main mass were used in immunohistochemical staining for the analysis             of TG-2 and pNF-κB expression. In the in vitro test, as the 4-HR concentrations             increased, the fraction of the bound complex NF-κB-inhibitory-κB (IκB) increased.             Consequently, the level of free IκB decreased. In the xenograft model, the cisplatin             plus 4-HR group exhibited a significantly decreased tumor growth rate than in             the saline group (P=0.039). The mean survival time of the cisplatin plus 4-HR             group was 51.20±3.96 days and was significantly prolonged compared with the other             groups (P<0.05). The body weight of the cisplatin plus 4-HR group had significantly             less weight loss than the cisplatin only group (P=0.045). In the immunohistochemical             analysis, the cisplatin plus 4-HR group had a significantly lower expression of             TG-2 and pNF-κB compared to the saline group (P<0.05). In conclusion, cisplatin             plus 4-HR combination therapy had clear advantages over the cisplatin only treatment             such as similar tumor growth inhibition compared to the cisplatin only treatment             despite the reduced dosage of cisplatin, less body weight loss, and prolonged             survival time.
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung 210-702, Republic of Korea. epker@chol.com
authors.forename: Seong-Gon
authors.initials: SG
authors.lastname: Kim
authors.forename: Sang-Woon
authors.initials: SW
authors.lastname: Lee
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Park
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Jeong
authors.forename: Je-Yong
authors.initials: JY
authors.lastname: Choi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006586:Hexanes / Q000494:pharmacology*; D006604:Hexylresorcinol; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D021381:Protein Transport / Q000187:drug effects; D011897:Random Allocation; D012118:Resorcinols / Q000494:pharmacology*; D011503:Transglutaminases / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D006586:Hexanes; D016328:NF-kappa B; D012118:Resorcinols; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D051550:I-kappa B Kinase; D019204:GTP-Binding Proteins; D002945:Cisplatin; D006604:Hexylresorcinol