title: Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch carcinogenesis by a 5-lipoxygenase inhibitor, garcinol.
abstract: Our previous studies have shown that aberrant arachidonic acid metabolism, especially the 5-lipoxygenase (5-Lox) pathway, is involved in oral carcinogenesis and can be targeted for cancer prevention. To develop potent topical agents for oral cancer chemoprevention, 5 known 5-Lox inhibitors from dietary and synthetic sources (Zileuton, ABT-761, licofelone, curcumin, and garcinol) were evaluated in silico for their potential efficacy. Garcinol, a polyisoprenylated benzophenone from the fruit rind of Garcinia spp., was found to be a promising agent based on the calculation of a theoretical activity index. Computer modeling showed that garcinol well fit the active site of 5-Lox, and potentially inhibited enzyme activity through interactions between the phenolic hydroxyl groups and the non-heme catalytic iron. In a short-term study on 7,12-dimethylbenz[a]anthracene (DMBA)-treated hamster cheek pouch, topical garcinol suppressed leukotriene B4 (LTB4) biosynthesis and inhibited inflammation and cell proliferation in the oral epithelium. In a long-term carcinogenesis study, topical garcinol significantly reduced the size of visible tumors, the number of cancer lesions, cell proliferation, and LTB4 biosynthesis. These results demonstrated that topical application of a 5-Lox inhibitor, garcinol, had chemopreventive effect on DMBA-induced hamster cheek pouch carcinogenesis.
authors.affiliation: School of Pharmaceutical & Life Sciences, Changzhou University, Jiangsu 213164, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Stomatological Hospital & School of Stomatology, Capital Medical University, 4 Tiantanxili, Dongcheng District, Beijing 100050, China.|Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Stomatological Hospital & School of Stomatology, Capital Medical University, 4 Tiantanxili, Dongcheng District, Beijing 100050, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA.
authors.forename: Joong-Youn
authors.initials: JY
authors.lastname: Shim
authors.affiliation: Center for Excellence in Post-Harvest Technologies, North Carolina A&T State University, North Carolina Research Campus, UNC Nutrition Research Building, Kannapolis, NC 28081.
authors.forename: Shengmin
authors.initials: S
authors.lastname: Sang
authors.affiliation: Stomatological Hospital & School of Stomatology, Capital Medical University, 4 Tiantanxili, Dongcheng District, Beijing 100050, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Chen
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D002273:Carcinogens; D049109:Cell Proliferation / Q000187:drug effects; D002610:Cheek; D006224:Cricetinae; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D010936:Plant Extracts; D013729:Terpenes / Q000008:administration & dosage*
chemical_list: D016588:Anticarcinogenic Agents; D002273:Carcinogens; D016859:Lipoxygenase Inhibitors; D010936:Plant Extracts; D013729:Terpenes; D007975:Leukotriene B4; D015127:9,10-Dimethyl-1,2-benzanthracene; C054597:garcinol