US EPA

1327345 

Journal Article 

Restoration of p53 tumor suppressor pathway in human cervical carcinoma cells by sodium arsenite 

Chou, RH; Huang, H 

2002 

Yes 

Biochemical and Biophysical Research Communications
ISSN: 0006-291X
EISSN: 1090-2104 

293 

1 

298-306 

English 

12054599 

10.1016/S0006-291X(02)00212-7 

WOS:000175514700046 

http://linkinghub.elsevier.com/retrieve/pii/S0006291X02002127
Exit
 

In most cervical cancer cells, p53 and Rb are disrupted by human papillomaviruses (HPVs) E6 and E7, respectively. Restoration of p53 or Rb function by blocking E6/p53 or E7/Rb pathway might be a potential therapeutic purpose for these cancer cells. Treatment with sodium arsenite (SA) resulted in significant repression of E6 and E7 mRNA levels in SiHa cells. After E6 and E7 repression, p53 was dramatically induced and accumulated in cellular nuclei and Rb was also induced. Two p53-responsive genes, p21(waf1/cip1) and mdm2, were induced after SA treatment. Furthermore, SA also reduced the expressions of Cdc25A and cyclin B, blocked cell cycle progression at G2/M phase, and induced apoptosis in SiHa cells. SA-induced apoptosis was greatly reduced by expression of a dominant-negative mutated p53. In this study, we have first demonstrated that SA did repress E6 and E7 oncogenes, restore the p53 tumor suppressor pathway and induce apoptosis in SiHa cells. Therefore, it would be a potential strategy to promote SA as therapeutic purpose for HPV-positive cancer cells. 

sodium arsenite; human papillomavirus; E6; E7; p53; Rb; apoptosis