Synergism of Rana catesbeiana ribonuclease and IFN-gamma triggers distinct death machineries in different human cancer cells.
Rana catesbeiana ribonuclease (RC-RNase) possesses tumor-specific cytotoxicity, which can be synergized by IFN-gamma. However, it is unclear how RC-RNase and RC-RNase/IFN-gamma induce cell death. In this study, we use substrate cleavage assays to systematically investigate RC-RNase- and RC-RNase/IFN-gamma-induced caspase activation in HL-60, MCF-7, and SK-Hep-1 cells. We find that RC-RNase and RC-RNase/IFN-gamma 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-gamma can kill different cancer cells by distinct mechanisms. Compared with onconase, RC-RNase seems to harbor a more specific anti-cancer activity.
Tang
Chih-Hang Anthony
CH
Neuromedical Scientific Center, Buddhist Tzu-Chi General Hospital, Hualien 970, Taiwan.
Hu
Chih-Chi Andrew
CC
Wei
Chyou-Wei
CW
Wang
Jaang-Jiun
JJ
D029845:Amphibian Proteins / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D045744:Cell Line, Tumor; D004357:Drug Synergism; D004722:Endoribonucleases / Q000494:pharmacology* / Q000633:toxicity; D007371:Interferon-gamma / Q000494:pharmacology* / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009369:Neoplasms / Q000201:enzymology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
D029845:Amphibian Proteins; D000970:Antineoplastic Agents; D007371:Interferon-gamma; D011065:Poly(ADP-ribose) Polymerases; D004722:Endoribonucleases; C094067:pyrimidine-guanine sequence-specific ribonuclease, Rana catesbeiana; D020169:Caspases