title: Gene induction by glycyrol to apoptosis through endonuclease G in tumor cells and prediction of oncogene function by microarray analysis.
abstract: Glycyrrhiza uralensis (Leguminosae) has long been known as an antiinflammatory agent for gastric ulcers, arthritis, and rheumatism. The flavonoid glycyrol (GC) (10 microg/ml) isolated from G. uralensis dramatically inhibits phorbol ester (phorbol 12-myristate 13-acetate)-induced nuclear factor (NF)-kappaB-dependent transcriptional activity, as determined by luciferase reporter activity in human kidney epithelial 293T cells. To investigate global gene expression profiling in cells by GC, we performed high-density oligonucleotide microarrays. Our microarray analyses showed that GC inhibited phorbol ester-induced NF-kappaB-dependent transcriptional activity in inflammatory-related gene expression. RT-PCR analysis, based on microarray data, showed that NF-kappaB-dependent genes (such as CCL2, CCL7, CD44, and HSPB8 in addition to NF-kappaB itself) were significantly downregulated by GC. Treatment with GC (10 microg/ml) inhibited I-kappaB degradation induced by phorbol 12-myristate 13-acetate. The microarray data also suggested that GC induces gene expression to p53-dependent apoptosis through endonuclease G, instead of CAD/DFF and AIF/PDCD8, as a downstream-apoptosis factor in human kidney epithelial 293T tumor cells, and induces oncogenes with a suppressor role as an added function.
authors.affiliation: Department of Oral Pathology, 2nd Stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Korea.
authors.forename: SungGa
authors.initials: S
authors.lastname: Lee
authors.forename: Hyun-Mee
authors.initials: HM
authors.lastname: Oh
authors.forename: Won-Bong
authors.initials: WB
authors.lastname: Lim
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Choi
authors.forename: Young-Na
authors.initials: YN
authors.lastname: Park
authors.forename: Jeong-Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Suk-Jin
authors.initials: SJ
authors.lastname: Hong
authors.forename: Hee-Kyun
authors.initials: HK
authors.lastname: Oh
authors.forename: Jong-Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Ok-Joon
authors.initials: OJ
authors.lastname: Kim
authors.forename: Hong-ran
authors.initials: HR
authors.lastname: Choi
authors.forename: Chang-Duk
authors.initials: CD
authors.lastname: Jun
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D020869:Gene Expression Profiling; D029882:Glycyrrhiza uralensis; D006801:Humans; D016328:NF-kappa B / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; C531349:glycyrol; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D013755:Tetradecanoylphorbol Acetate