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Enhanced cellular radiation sensitivity of androgen-independent human prostate tumor cells by onconase
1Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. ilee2@mail.med.upenn.edu
Abstract:
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.
Insights
Onconase, derived from amphibian oocytes, reduces cellular oxygen consumption (QO2) in cancer cells. This finding suggests onconase may enhance radiation therapy effectiveness, particularly for prostate cancer.
Area of Science:
- Biochemistry
- Oncology
- Cell Biology
Background:
- Amphibian-derived onconase is known to increase tumor oxygen levels.
- The mechanism by which onconase affects cellular oxygen consumption (QO2) is not fully understood.
Purpose of the Study:
- To investigate the effect of onconase on cellular oxygen consumption (QO2) in 9L rat glioma and DU145 human prostate adenocarcinoma cells.
- To determine if onconase enhances radiation sensitivity in androgen-insensitive prostate cancer cells.
Main Methods:
- Cellular oxygen consumption (QO2) was measured using a Clark-type electrode chamber.
- Radiation sensitivity assays were performed on DU145 cells treated with varying concentrations of onconase.
Main Results:
- Onconase significantly inhibited QO2 in both 9L rat glioma and DU145 human prostate adenocarcinoma cells.
- Radiation sensitization was observed in DU145 cells at onconase concentrations greater than 5 micrograms/ml, irrespective of p53 status.
Conclusions:
- Onconase reduces cellular oxygen consumption, potentially increasing oxygen availability to hypoxic tumor cells.
- Onconase demonstrates potential as a radiosensitizer for androgen-insensitive prostate cancer, warranting further in vivo investigation.