Synergism of Rana catesbeiana ribonuclease and IFN-γ triggers distinct death machineries in different human cancer cells

Rana catesbeiana ribonuclease (RC-RNase) possesses tumor-specific cytotoxicity, which can be synergized by IFN-γ. However, it is unclear how RC-RNase and RC-RNase/IFN-γ induce cell death. In this study, we use substrate cleavage assays to systematically investigate RC-RNase- and RC-RNase/IFN-γ-induc...

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Bibliographic Details
Published in:FEBS letters 2005-01, Vol.579 (1), p.265-270
Main Authors: Tang, Chih-Hang Anthony, Hu, Chih-Chi Andrew, Wei, Chyou-Wei, Wang, Jaang-Jiun
Format: Article
Language:English
Subjects:
Amphibian Proteins - pharmacology
Amphibian Proteins - toxicity
Animals
Anti-tumor ribonuclease
Antineoplastic Agents - pharmacology
Antineoplastic Agents - toxicity
Caspase
Caspases - metabolism
Cell Death
Cell Line, Tumor
Drug Synergism
Endoribonucleases - pharmacology
Endoribonucleases - toxicity
Interferon-gamma - pharmacology
Interferon-gamma - toxicity
Mitochondria - drug effects
Mitochondria - enzymology
Neoplasms - enzymology
Onconase
PARP
poly(ADP-ribose) polymerase
Poly(ADP-ribose) Polymerases - metabolism
Rana catesbeiana
Rana catesbeiana ribonuclease
RC-RNase
sodium 3′-[1-(phenylamino-carbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro)benzene sulfonic acid hydrate
XTT
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Summary:Rana catesbeiana ribonuclease (RC-RNase) possesses tumor-specific cytotoxicity, which can be synergized by IFN-γ. However, it is unclear how RC-RNase and RC-RNase/IFN-γ induce cell death. In this study, we use substrate cleavage assays to systematically investigate RC-RNase- and RC-RNase/IFN-γ-induced caspase activation in HL-60, MCF-7, and SK-Hep-1 cells. We find that RC-RNase and RC-RNase/IFN-γ induce mitochondria-mediated caspase activation in HL-60 and MCF-7 cells but not in SK-Hep-1 cells, although death of SK-Hep-1 cells is closely related to mitochondrial disruptions. Our findings provide evidence that RC-RNase and RC-RNase/IFN-γ can kill different cancer cells by distinct mechanisms. Compared with onconase, RC-RNase seems to harbor a more specific anti-cancer activity.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2004.11.086