Inhibition of proliferative activity of pulmonary fibroblasts by tetrandrine

Details

• Personal Author:
  Castranova, Vincent ; Dey RD ; Durham JP ; Reist RH ; Rojanasakul Y
• Description:
  The effects of tetrandrine (518343) on the proliferative activity of pulmonary fibroblasts were examined to determine if the antifibrotic action of tetrandrine might result from an ability to inhibit fibroblast proliferation. Human fetal lung fibroblasts were incubated with 0 to 11 micromolar (microM) tetrandrine for 6 hours (hr), 0 to 18hr after being stimulated with human serum or plasma plus 50 nanograms per milliliter (ml) platelet derived growth factor (PGDF), tumor necrosis factor alpha (TNFa), or basic fibroblast growth factor (bFGF). The extent of fibroblast proliferation was determined by measuring uptake of tritiated thymidine. Tetrandrine significantly inhibited fibroblast proliferation when added immediately after treatment with PGDF, bFGF, and TNFa in plasma and serum in a concentration dependent manner, the concentrations causing 50% inhibition (IC50s) being 2.5, 1.5, 2.5, and 3.5microM, respectively. Inhibitory effects persisted for up to 14hr after stimulation with the growth factors. Tetrandrine had no effect on fibroblast viability, as no cell killing was detected when the trypan-blue test was applied. Tetrandrine also did not affect cell morphology. Pulmonary fibroblasts stimulated with human serum were treated with 100microM of the calcium (Ca+2) channel blockers nitrendipine or verapamil or the cytoskeletal modifiers cytochalasin- B at 0 to 20 micrograms per milliliter (microg/ml) or taxol at 0 to 20microM. The effects on cellular proliferation were determined. Nitrendipine and cytochalasin-B significantly inhibited fibroblast proliferation in a concentration dependent manner, the IC50s being 25microM and 3.5microg/ml. Cytochalasin-B also caused significant structural deformation of the fibroblasts. Taxol and verapamil did not affect fibroblast proliferation. The authors conclude that tetrandrine directly inhibits proliferation of lung fibroblasts, an effect not explained by Ca+2 channel blockade or modification of the cytoskeletal system. The antifibrotic activity of tetrandrine may be mediated, by a direct inhibition of fibroblastic activity that normally occurs during the development of silicosis. [Description provided by NIOSH]
• Subjects:
  Biopharmaceutics Cell Division Growth Lung Occupational Health Respiratory System Safety
• Keywords:
  Cell-division Dose-response Fibrogenesis Growth-factors Growth-inhibition In-vitro-studies Lung-cells Natural-products NIOSH-Author Pharmaceuticals
• ISSN:
  0041-008X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DRDS - Division of Respiratory Disease Studies
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  70-76
• Volume:
  122
• Issue:
  1
• NIOSHTIC Number:
  nn:00232199
• Citation:
  Toxicol Appl Pharmacol 1993 Sep; 122(1):70-76
• Contact Point Address:
  V. Castranova, Division of Respiratory Disease Studies, National lnstitute for Occupational Safety and Health, Morgantown, West Virginia 26505
• CAS Registry Number:
  Tetrandrine (CAS RN 518-34-3)
• Federal Fiscal Year:
  1993
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:666d31b5c69e28cd50397ef146d856a88df1afa6040f70a8fb986a886ec1247ea3f7044d82291255648831f88765c9c543c915c57564e3dda5ad6e836b9fa91a
• Download URL:
  https://stacks.cdc.gov/view/cdc/204955/cdc_204955_DS1.pdf
• File Type:
  [PDF - 530.78 KB ]