Effects of uwhangchungsimwon on cell viability, proliferation, and gene expression of human neuronal cell line IMR32

Am J Chin Med. 2001;29(3-4):445-58. doi: 10.1142/S0192415X01000460.

Abstract

Uwhangchungsimwon (pill, UC) is one of the traditional Korean medical prescriptions that has been most frequently used for stroke. To characterize the effects of UC on human neuronal cells, the human neuroblastoma cell line IMR32 was treated with UC, and cell viability, cell proliferation, apoptosis, and gene expression were analyzed. The effect of UC on recovery of cell viability was analyzed following stress induction by nutrient depletion or cold shock. Flow cytometric analysis of the cell cycle showed that UC inhibits cell cycle progression of IMR32 in a dose- and time-dependent manner. UC was also identified to increase cell viability and suppress apoptosis induction by a DNA-damaging agent, etoposide. Quantitative RT-PCR analysis revealed that expressions of the p53 tumor suppressor gene and its downstream effect, Waf1, are stimulated whereas expressions of positive cell cycle regulators, c-Myc, c-Fos, and Cyclin D1 were repressed by UC treatment. Moreover, while expression levels of apoptosis inhibitors, Bcl-2 and Bcl-XL were increased following UC treatment, that of an apoptosis promoter, Bax, was decreased. In addition, expression of BMP-7, which has been recently demonstrated to improve the motor neuron recovery from stroke, was induced by UC while it was not detected in untreated cells. Taken together, our data suggest that the pharmacoclinical effects of UC might be derived in part from its negative regulation of cell proliferation and apoptosis through the transcriptional control of related genes.

MeSH terms

  • Apoptosis / drug effects
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / genetics
  • Cell Cycle
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Cyclin D1 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics
  • Drugs, Chinese Herbal / pharmacology*
  • Gene Expression / drug effects*
  • Genes, fos
  • Genes, myc
  • Histones / genetics
  • Humans
  • Neuroblastoma
  • Neurons / cytology
  • Neurons / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Plants, Medicinal*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Stroke
  • Transcription, Genetic
  • Transforming Growth Factor beta*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • bcl-2-Associated X Protein
  • bcl-X Protein

Substances

  • BAX protein, human
  • BCL2L1 protein, human
  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Drugs, Chinese Herbal
  • Histones
  • Neuroprotective Agents
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Transforming Growth Factor beta
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • uwhangchungsimwon
  • Cyclin D1