Restoration of p53 tumor suppressor pathway in human cervical carcinoma cells by sodium arsenite.
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.
Chou
Ruey-Hwang
RH
Department of Life Science, National Tsing-Hua University, HsinChu 30043, Taiwan, ROC.
Huang
Haimei
H
D017209:Apoptosis / Q000187:drug effects; D018053:Arsenites / Q000494:pharmacology*; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016158:Genes, p53 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009336:Necrosis; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D011419:Propidium / Q000494:pharmacology; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017670:Sodium Compounds / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
D018053:Arsenites; D017931:DNA Primers; C068651:E6 protein, Human papillomavirus type 16; D004791:Enzyme Inhibitors; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D017670:Sodium Compounds; C059731:oncogene protein E7, Human papillomavirus type 16; D011419:Propidium; C017947:sodium arsenite