Gene induction by glycyrol to apoptosis through endonuclease G in tumor cells and prediction of oncogene function by microarray analysis.
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.
Lee
SungGa
S
Department of Oral Pathology, 2nd Stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Korea.
Oh
Hyun-Mee
HM
Lim
Won-Bong
WB
Choi
Eun-Ju
EJ
Park
Young-Na
YN
Kim
Jeong-Ah
JA
Choi
Ji-Young
JY
Hong
Suk-Jin
SJ
Oh
Hee-Kyun
HK
Son
Jong-Keun
JK
Lee
Seung-Ho
SH
Kim
Ok-Joon
OJ
Choi
Hong-ran
HR
Jun
Chang-Duk
CD
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
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