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Arsenic trioxide induces cervical cancer apoptosis, but specifically targets human papillomavirus-infected cell populations.
MedLine Citation:
PMID:  22245994     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVES: Human papillomavirus (HPV) is directly associated with the occurrence and development of cervical cancer. Targeting HPV infection has become the priority in treatment and prevention. Some treatment strategies have shown a limited therapeutic potential in suppressing and reversing the oncogenic effects of HPVs, but are compromised by the toxicity, immune suppression and the expense. Arsenic trioxide (As2O3) has shown therapeutic efficacy in the treatment of haematological and solid cancer and has been demonstrated to effectively induce apoptosis of HPV-infected cervical cancer cells in vitro. Here, we examined the effects and possible molecular pathway of As2O3-induced apoptosis in HPV-infected and noninfected cervical cancer cells. METHODS: As2O3 was added to HPV-infected cell lines HeLa and CaSki and the HPV-negative cell line C33A at concentrations from 1 to 10 µmol/l. Cell proliferation rates were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays after exposure. Expressions of tumour suppressor gene p53, activated caspase-3 and cell cycle distribution were evaluated in relation to HPV-E6 protein expression by confocal microscopy immunofluorescent staining and flow cytometry. RESULTS: As2O3 reduced cell populations by 16% in C33A but by 48-60% in HPV-infected cell lines CaSki and HeLa. The expression of HPV-E6 proteins was drastically down-regulated in a dose-dependent manner, whereas p53 and activated caspase-3 expressions increased in the HPV-infected cell lines. Flow cytometry demonstrated cell cycle arrest in S-G2/M phases, and increasing apoptotic bodies were seen in HPV-infected lines only. CONCLUSION: As2O3, at low concentrations, inhibited HPV-E6 protein expression, leading to up-regulated p53 levels, induced S to G2/M arrest and apoptosis.
Authors:
Xuesong Wen; Dong Li; Yunyan Zhang; Shiping Liu; Lucy Ghali; Ray K Iles
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-12
Journal Detail:
Title:  Anti-cancer drugs     Volume:  -     ISSN:  1473-5741     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
aCentre for Investigative and Diagnostic Oncology, Middlesex University, London bFaculty of Health Social Care and Education, Anglia Ruskin University, Chelmsford, UK c1st Affiliated Hospital of Harbin Medical University d3rd Affiliated Hospital of Harbin Medical University, Harbin, China.
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