Role of p53 in antioxidant defense of HPV-positive cervical carcinoma cells following H2O2 exposure.
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.
Ding
Boxiao
B
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Chi
Sung Gil
SG
Kim
Se Heon
SH
Kang
Suki
S
Cho
Jae Ho
JH
Kim
Dong Su
DS
Cho
Nam Hoon
NH
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000975:Antioxidants / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D052162:Human papillomavirus 16; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D030361:Papillomavirus Infections / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
D000975:Antioxidants; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D016877:Oxidants; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine