Inhibition of human smooth muscle cell proliferation by gamigeonsim-tang through the transcriptional regulation of cell cycle-controlling genes.
The effects of gamigeonsim-tang (GGT) on cellular proliferation and expression of cell cycle-related genes were investigated in human smooth muscle cell HISM. HISM cells were treated with an aqueous extract of GGT. Cellular proliferation was investigated by an immunocytometric analysis of PCNA expression and a flow cytometric analysis of the cell cycle progression. Reduced expression of PCNA and a significant accumulation of G1 phase cells were observed following treatment, indicating that GGT inhibits cellular proliferation of human smooth muscle cells. To explore whether GGT affects the transcription of cell cycle-regulating genes, we evaluated mRNA expression of p53, p21Waf1 PCNA, Cyclin D1, Cdc2, Histone H3, c-Myc, and c-Fos using a quantitative RT-PCR analysis. While increased expressions of two negative cell cycle regulators, p53 and p21Waf1 were found, reduced expressions of cell cycle stimulators, PCNA, c-Fos, and c-Myc, were identified following treatment. Taken together, our study demonstrates that GGT inhibits cellular proliferation of human smooth muscle cell through the up- and down-regulation of growth-inhibiting and growth-promoting genes, respectively.
Ko
S G
SG
Department of Circulatory Internal Medicine, College of Oriental Medicine, Kyung-Hee University, Seoul, Korea.
Lee
K S
KS
Cho
K H
KH
Kim
Y S
YS
Bae
H S
HS
Moon
S K
SK
D016203:CDC2 Protein Kinase / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D018816:Genes, cdc; D006657:Histones / Q000235:genetics; D006801:Humans; D007723:Korea; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004365:Drugs, Chinese Herbal; D006657:Histones; D018809:Proliferating Cell Nuclear Antigen; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D016203:CDC2 Protein Kinase