Differing Roles of Protein Kinase C on the Antiproliferative Effects of Tumor Necrosis Factor Alpha and Beta on LoVo Cells

Authors:
  • NMNagahide Matsubara
    Nagahide Matsubara
  • SFSadanori Fuchimoto
    Sadanori Fuchimoto
  • KOKunzo Orita
    Kunzo Orita
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Abstract
In this study we examined whether the antiproliferative effects of tumor necrosis factor (TNF)-α and – β were associated with the activation of protein kinase C (PKC), using the LoVo human colon cancer cell line which is resistant to both TNFs. In combination with 12–0-tetradecanoylphorbol-13-acetate (TPA), a potent activator of PKC, TNF-α caused marked growth inhibition of LoVo cells, but TNF- β had little antiproliferative effect. There was no difference in the effect when TPA was added 1 h before or 4 h after TNF-α administration. A PKC inhibitor, H-7, not only decreased the sensitivity of LoVo cells to TNF-α but also caused a slight promotion of cell proliferation and dose-dependently blocked the growth inhibition induced by TNF-α and TPA. These results suggested a possible regulatory function of PKC within the TNF-α-mediated intracellular signalling pathway. PKC may act at a later stage in the transduction pathway.

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