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Role of p53 in antioxidant defense of HPV-positive cervical carcinoma cells following H2O2 exposure

 Boxiao Ding  ;  Sung Gil Chi  ;  Nam Hoon Cho  ;  Dong Su Kim  ;  Jae Ho Cho  ;  Suki Kang  ;  Se Heon Kim 
 JOURNAL OF CELL SCIENCE, Vol.120(pt13) : 2284-2294, 2007 
Journal Title
Issue Date
Antioxidants/metabolism ; DNA Damage/drug effects ; Deoxyguanosine/analogs & derivatives ; Deoxyguanosine/metabolism ; Down-Regulation/drug effects ; Female ; HeLa Cells ; Human papillomavirus 16* ; Humans ; Hydrogen Peroxide/metabolism ; Hydrogen Peroxide/pharmacology* ; Oncogene Proteins, Viral/metabolism ; Oxidants/metabolism ; Oxidants/pharmacology* ; Oxidation-Reduction/drug effects ; Oxidative Stress/drug effects ; Papillomavirus Infections/metabolism* ; Repressor Proteins/metabolism ; Tumor Suppressor Protein p53/metabolism* ; Uterine Cervical Neoplasms/metabolism*
p53 ; SiHa ; H2O2 ; ROS ; Oxidative stress ; RNAinterference (RNAi)
In HPV-positive cervical carcinoma cells, p53 protein is functionally antagonized by the E6 oncoprotein. We investigated a possible role of p53 in antioxidant defense of HPV-positive cervical cancer cell lines. We found that SiHa cells containing integrated HPV 16 had higher expression of p53 and exhibited the greatest resistant to H2O2-induced oxidative damage, compared with HeLa, CaSki and ME180 cell lines. Downregulation of p53 resulted in the inhibition of p53-regulated antioxidant enzymes and elevated intracellular ROS in SiHa cells. By contrast, the ROS level was not affected in HeLa, CaSki and ME180 cell lines after inhibition of the p53 protein. Under mild or severe H2O2-induced stress, p53-deficient SiHa cells exhibited much higher ROS levels than control SiHa cells. Furthermore, we analyzed cell viability and apoptosis after H2O2 treatment and found that p53 deficiency sensitized SiHa cells to H2O2 damage. Inhibition of p53 resulted in excessive oxidation of DNA; control SiHa cells exhibited a more rapid removal of 8-oxo-7,8-dihydro-2′-deoxyguanosine from DNA compared with p53-deficient SiHa cells exposed to the same level of H2O2 challenge. These data collectively show that endogenous p53 in SiHa cells has an antioxidant function and involves in the reinforcement of the antioxidant defense.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Kang, Suki(강숙희) ORCID logo https://orcid.org/0000-0002-9957-3479
Kim, Se Heon(김세헌)
Cho, Nam Hoon(조남훈) ORCID logo https://orcid.org/0000-0002-0045-6441
Cho, Jae Ho(조재호) ORCID logo https://orcid.org/0000-0001-9966-5157
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