Antisense of human peroxiredoxin II enhances radiation-induced cell death.
Human peroxiredoxin II (Prx II) has been known to function as an antioxidant enzyme in cells. Using head-and-neck cancer cell lines, we investigated whether Prx II expression is related to the resistance of cells to radiation therapy in vivo and in vitro, and whether a Prx II antisense serves as a radiosensitizer. Increased expression of Prx II was observed in tissues isolated from the patients who did not respond to radiation therapy, whereas Prx II expression was weak in tissues from the patients with regressed tumors. Enhanced expression of Prx II in UMSCC-11A (11A) cells was also observed after treatment with gamma radiation. This increased expression conferred radiation resistance to cancer cells because overexpression of Prx II protected 11A cells from radiation-induced cell death, suggesting that blocking Prx II expression could enhance radiation sensitivity. Treatment of 11A cells with a Prx II antisense decreased induction of Prx II, enhancing the radiation sensitivity. From these results, we suggest that stress-induced overexpression of Prx II increases radiation resistance via protection of cancer cells from radiation-induced oxidative cytolysis and that a Prx II antisense can be used as a radiosensitizer.
Park
S H
SH
Laboratory of Experimental Therapeutics, Korea Cancer Center Hospital, Seoul.
Chung
Y M
YM
Lee
Y S
YS
Kim
H J
HJ
Kim
J S
JS
Chae
H Z
HZ
Yoo
Y D
YD
D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015152:Blotting, Northern; D016923:Cell Death / Q000187:drug effects; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D015151:Immunoblotting; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D010544:Peroxidases / Q000378:metabolism / Q000627:therapeutic use*; D054464:Peroxiredoxins; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D016376:Oligonucleotides, Antisense; D011838:Radiation-Sensitizing Agents; D010544:Peroxidases; D054464:Peroxiredoxins