STAT-1-independent upregulation of FADD and procaspase-3 and -8 in cancer cells treated with cytotoxic drugs

Biochem Biophys Res Commun. 1999 Mar 24;256(3):603-7. doi: 10.1006/bbrc.1999.0391.

Abstract

We have previously shown that treatment by anticancer drugs sensitized tumor cells to Fas (APO-1/CD95)-mediated cell death. The present study demonstrates that the cytotoxic drugs cisplatin, doxorubicin and mitomycin C induce the accumulation of the Fas receptor, the FADD adaptor molecule, the procaspases-8, -3 and -2L and the proapoptotic molecule Bax in several human colon cancer cells. This upregulation is also observed in U3A myeloblastoma cells that do not express STAT-1, a transcription factor involved in the constitutive expression of procaspases. We conclude that anticancer drugs sensitize tumor cells to Fas-mediated cell death by a STAT-1-independent upregulation of molecules involved in this apoptotic pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Caspase 2
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism*
  • Cisplatin / pharmacology
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Dactinomycin / pharmacology
  • Doxorubicin / pharmacology
  • Enzyme Precursors / metabolism*
  • Fas-Associated Death Domain Protein
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Isoenzymes / metabolism
  • Mitomycin / pharmacology
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • RNA, Messenger / metabolism
  • Receptors, Tumor Necrosis Factor / physiology
  • STAT1 Transcription Factor
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Up-Regulation / drug effects*
  • bcl-2-Associated X Protein
  • fas Receptor

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • BAX protein, human
  • Carrier Proteins
  • DNA-Binding Proteins
  • Enzyme Precursors
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Isoenzymes
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Trans-Activators
  • bcl-2-Associated X Protein
  • fas Receptor
  • Dactinomycin
  • Mitomycin
  • Doxorubicin
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 2
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases
  • Cisplatin