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Chemically modified tetracyclines induce cytotoxic effects against J774 tumour cell line by activating the apoptotic

Pietro D'Agostino1, Viviana Ferlazzo, Salvatore Milano

  • 1Department of Immuno-Haematology and Transfusion, University of Palermo, Palermo, Italy.

International Immunopharmacology
|January 23, 2003
PubMed

Insights

Chemically modified tetracyclines (CMTs) induce programmed cell death (PCD) in J774 macrophages. CMTs activate caspase-8 and caspase-9, increasing Bcl-2 and c-myc mRNA, suggesting potential anti-tumor properties.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Pharmacology

Background:

  • Chemically modified tetracyclines (CMTs) are being investigated for their therapeutic potential.
  • Understanding the mechanisms of programmed cell death (PCD) is crucial for developing new treatments.

Purpose of the Study:

  • To investigate the effects of CMTs on apoptosis in J774 macrophage cell line.
  • To elucidate the role of caspase cascades and gene expression in CMT-induced PCD.

Main Methods:

  • Acridine orange/ethidium bromide staining
  • TUNEL assay
  • Fragmentation ELISA
  • Flow cytometry for cell cycle analysis
  • Caspase inhibition assays (Z-VAD-fmk, Z-IEDT-fmk, Z-LEHD-fmk)
  • mRNA expression analysis (Bcl-2, c-myc)

Main Results:

  • CMTs induced morphological and biochemical hallmarks of apoptosis in J774 cells.
  • Flow cytometry revealed an apoptotic sub-G0G1 peak, indicating PCD.
  • CMT-8 demonstrated the strongest apoptotic effect in a dose-dependent manner.
  • CMTs activated caspase-8 and partially caspase-9, confirmed by specific inhibitors.
  • CMTs upregulated Bcl-2 and c-myc mRNA expression.

Conclusions:

  • CMTs effectively trigger apoptosis in macrophages through caspase activation.
  • Modulation of Bcl-2 and c-myc mRNA expression is involved in CMT-induced PCD.
  • CMTs exhibit potential as anti-tumor agents due to their ability to induce apoptosis.

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