Enhanced cellular radiation sensitivity of androgen-independent human prostate tumor cells by onconase.
The RNase-like onconase, isolated from amphibian oocytes, showed increases in median tumor pO2 in solid tumors (1). This led us to consider if onconase could decrease cellular O2 consumption (QO2) on 9L rat glioma as well as DU145 human prostate adenocarcinoma cells. Using a Clark-type electrode chamber, we observed that onconase significantly inhibited QO2 in both tumors we tested. Since onconase-induced reduction in QO2 could lead to increases in radiation sensitivity, due to the diffusion of O2 to previously hypoxic tumor cells, we used androgen-insensitive DU145 cells to study onconase-induced changes in radiation sensitivity in vitro. Radiation sensitization was achieved with > 5 micrograms/ml of onconase, regardless of the p53 status of tumor cells. Data presented here suggested that onconase-induced enhancement in radiation sensitization in vitro of androgen-insensitive prostate cancer cells warranted further studies of radiation responses in vivo, prior to clinical settings for the advanced-stages of prostate cancer.
Lee
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I
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. ilee2@mail.med.upenn.edu
Lee
Y H
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Mikulski
S M
SM
Lee
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Shogen
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K
D000230:Adenocarcinoma; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001932:Brain Neoplasms; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004527:Egg Proteins / Q000633:toxicity*; D005910:Glioma; D006801:Humans; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D011471:Prostatic Neoplasms; D011836:Radiation Tolerance / Q000187:drug effects*; D051381:Rats; D012260:Ribonucleases / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000970:Antineoplastic Agents; D004527:Egg Proteins; D016159:Tumor Suppressor Protein p53; D012260:Ribonucleases; C058703:ranpirnase