title: Suppression of the TNF-alpha level is mediated by Gan-Lu-Yin (traditional Chinese medicine) in human oral cancer cells through the NF-kappa B, AKT, and ERK-dependent pathways.
abstract: Oral cancer is one of the major causes of deaths in the male population of Taiwan. Gan-Lu-Yin (GLY) is used for an adjuvant treatment of Traditional Chinese Medicine in clinical patients. In this study, we investigated the molecular mechanisms in oral cancer cell lines after exposure to GLY. The cytometric bead-based array (CBA) method was used for the examining and analyzing of tumor necrosis factor-alpha (TNF-α) secretion level. TNF-α mRNA expression was determined by real-time PCR analysis. Nuclear factor kappa B (NF-κB) activity and other relative proteins were determined by NF-κB promoter assay, Western blotting, electrophoretic mobility shift assay (EMSA), and immuno-staining analyses. GLY decreased the secretion of TNF-α from the oral cancer CAL 27 cells. Furthermore, 2000 μg/mL of GLY significantly suppressed TNF-α mRNA expression of CAL 27 cells in a time-dependent manner. GLY reduced the levels of proteins, including nuclear NF-κB (p65 and p50), p-IKK (ser176), p-IκB, p-AKT, p-ERK, and nuclear Egr-1 in a time and dose-dependent manner. GLY also suppressed the NF-κB activity and translocation in CAL 27 cells. We suggest that GLY might promote the cure of oral cancer through decreasing the level of TNF-α cytokine, and these actions were mediated partially through the NF-κB, AKT, and ERK-dependent pathways in vitro. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1196-1205, 2016.
authors.affiliation: Department of Pharmacology, China Medical University, Taichung, 404, Taiwan.
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Wu
authors.affiliation: School of Pharmacy, China Medical University, Taichung, 404, Taiwan.
authors.forename: Hong-Zin
authors.initials: HZ
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, China Medical University, Taichung, 404, Taiwan.
authors.forename: Wen-Tsong
authors.initials: WT
authors.lastname: Hsieh
authors.affiliation: Department of Nutrition, China Medical University, Taichung, 404, Taiwan.
authors.forename: Feng-Yao
authors.initials: FY
authors.lastname: Tang
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, 404, Taiwan.|Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, 404, Taiwan.
authors.forename: Da-Tian
authors.initials: DT
authors.lastname: Bau
authors.affiliation: College of Medicine and Life Science, Chung Hwa University of Medical Technology, Tainan County, 717, Taiwan.|School of Medicine, China Medical University Hospital, Taichung, 404, Taiwan.
authors.forename: Kuang-Chi
authors.initials: KC
authors.lastname: Lai
authors.affiliation: School of Pharmacy, China Medical University, Taichung, 40402, Taiwan.
authors.forename: Jin-Cherng
authors.initials: JC
authors.lastname: Lien
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.|Department of Biotechnology, Asia University, Taichung, 413, Taiwan.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008516:Medicine, Chinese Traditional; D008856:Microscopy, Fluorescence; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013624:Taiwan; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004365:Drugs, Chinese Herbal; D020672:I-kappa B Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
keywords: AKT; ERK-dependent pathways; Gan-Lu-Yin; NF-κB; TNF-α; cytokines; traditional Chinese medicine