Cancer Immunology, Immunotherapy

, Volume 40, Issue 4, pp 228–234 | Cite as

Inhibitory effects of tamoxifen and tumor necrosis factor α on human glioblastoma cells

  • Koichi Iwasaki
  • Steven A. Toms
  • Gene H. Barnett
  • Melinda L. Estes
  • Manjula K. Gupta
  • Barbara P. Barna
Original Article Tumor Necrosis Factor α, Tamoxifen, Protein Kinase C Inhibitor, Apoptosis, Human Glioblastoma

Abstract

We reported previously that tumor necrosis factor α (TNFα) inhibited proliferation and invasiveness of human malignant glial cells. Because tamoxifen, an estrogen antagonist, has also been shown to inhibit growth of such cells, we hypothesized that a combination of tamoxifen and TNFα might be more effective than either reagent alone. TNFα (1–100 ng/ml) or tamoxifen (80 ng/ml-2 μg/ml) alone inhibited proliferation of a human glioblastoma cell line (WITG3) in a dose-dependent fashion; in combination, tamoxifen and TNFα yielded additive growth inhibition. Apoptotic cells characterized by nuclear fragmentation were detectable after 48 h of TNFα or tamoxifen exposure and were significantly increased by combination treatment. In non-neoplastic human astroglia and fibroblasts, proliferation was unaffected by tamoxifen, and enhanced by TNFα as previously reported. Staurosporine (2–50 nM), which has been reported to augment the effects of TNFα, was less effective than tamoxifen against WITG3 and, in addition, was markedly inhibitory to non-neoplastic glial cells. Binding studies yielded no evidence of WITG3 estrogen or progesterone receptors, nor of tamoxifen effects on TNFα receptors. Data suggest that TNFα and tamoxifen in combination display growth-regulatory properties, which (a) are more inhibitory to human glioblastoma cells than either agent alone, (b) do not affect non-neoplastic glia, (c) do not require either estrogen/ progesterone receptors or alteration of external TNFα receptors, and (d) may involve apoptosis.

Key words

Tumor necrosis factor α Tamoxifen Protein kinase C inhibitor Apoptosis Human glioblastoma 

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Koichi Iwasaki
    • 1
  • Steven A. Toms
    • 2
  • Gene H. Barnett
    • 2
  • Melinda L. Estes
    • 3
  • Manjula K. Gupta
    • 4
  • Barbara P. Barna
    • 4
  1. 1.Section of Neuro-oncology, Department of NeurologyThe Cleveland Clinic FoundationClevelandUSA
  2. 2.Department of NeurosurgeryThe Cleveland Clinic Foundation, ClevelandUSA
  3. 3.Department of Anatomic PathologyThe Cleveland Clinic FoundationClevelandUSA
  4. 4.Department of Clinical Pathology/L 12The Cleveland Clinic FoundationClevelandUSA

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