title: Expression of a splice variant of CYP26B1 in betel quid-related oral cancer.
abstract: Betel quid (BQ) is a psychostimulant, an addictive substance, and a group 1 carcinogen that exhibits the potential to induce adverse health effects. Approximately, 600 million users chew a variety of BQ. Areca nut (AN) is a necessary ingredient in BQ products. Arecoline is the primary alkaloid in the AN and can be metabolized through the cytochrome P450 (CYP) superfamily by inducing reactive oxygen species (ROS) production. Full-length CYP26B1 is related to the development of oral pharyngeal cancers. We investigated whether a splice variant of CYP26B1 is associated with the occurrence of ROS related oral and pharyngeal cancer. Cytotoxicity assays were used to measure the effects of arecoline on cell viability in a dose-dependent manner. In vitro and in vivo studies were conducted to evaluate the expression of the CYP26B1 splice variant. The CYP26B1 splice variant exhibited lower expression than did full-length CYP26B1 in the human gingival fibroblast-1 and Ca9-22 cell models. Increased expression of the CYP26B1 splice variant was observed in human oral cancer tissue compared with adjacent normal tissue, and increased expression was observed in patients at a late tumor stage. Our results suggested that the CYP26B1 splice variant is associated with the occurrence of BQ-related oral cancer.
authors.affiliation: School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan ; Cancer Center, Kaohsiung Medical University Hospital, No. 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan.
authors.forename: Ping-Ho
authors.identifier: 0000-0002-0357-8081
authors.initials: PH
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, Kaohsiung Medical University Hospital, No. 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan ; Department of Otolaryngology, College of Medicine, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan.
authors.forename: Ka-Wo
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-sen University, No. 70 Lienhai Road, Kaohsiung 80424, Taiwan.
authors.forename: Cheng-Chieh
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan.
authors.forename: Jeff Yi-Fu
authors.initials: JY
authors.lastname: Chen
authors.affiliation: School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan ; Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan.
authors.forename: Yan-Hsiung
authors.initials: YH
authors.lastname: Wang
authors.affiliation: School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan ; Division of Conservative Dentistry, Department of Dentistry, Kaohsiung Medical University Hospital, No. 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan.
authors.forename: Ker-Kong
authors.identifier: 0000-0001-6474-0372
authors.initials: KK
authors.lastname: Chen
authors.affiliation: Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan.
authors.forename: Hui-Min David
authors.initials: HM
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-sen University, No. 70 Lienhai Road, Kaohsiung 80424, Taiwan.
authors.forename: Hurng-Wern
authors.identifier: 0000-0001-5015-3708
authors.initials: HW
authors.lastname: Huang
authors.affiliation: Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan ; Department of Biological Sciences, National Sun Yat-sen University, No. 70 Lienhai Road, Kaohsiung 80424, Taiwan.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
mesh_terms: D017398:Alternative Splicing; D001114:Areca / Q000737:chemistry; D001115:Arecoline / Q000009:adverse effects; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006801:Humans; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000235:genetics*; D000072516:Retinoic Acid 4-Hydroxylase
chemical_list: D002273:Carcinogens; D001115:Arecoline; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase