Apicidin down-regulates human papillomavirus type 16 E6 and E7 transcripts and proteins in SiHa cervical cancer cells.
Virtually all cervical cancer morbidities are associated with genital skin or mucosa cell infection with human papillomavirus (HPV). The HPV oncogenic proteins E6 and E7 are able to inactivate p53 and Rb proteins, which results in malignant transformation. Employing quantitative real-time PCR and Western blot analysis, we observed that apicidin histone deacetylase (HDAC) inhibitor significantly reduced HPV16-E6 and -E7 transcripts and protein levels in SiHa cervical cancer cells. Moreover, we found that apicidin lowered HPV16-E6 and -E7 transcript stability and significantly decreased these transcripts' half-life from approximately 5h to 2h and from 6h to 3h, respectively. Our results from experiments with protein biosynthesis inhibitor suggest the involvement of an RNase and/or mRNA stabilization protein in HPV16-E6 and -E7 transcript stabilization. Since the HPV type 16 is associated with most cervical cancer incidence and HDAC inhibitors are being tested in anti-cancer clinical trials, our observations may have clinical significance.
Luczak
Michał W
MW
Poznań University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego Street, 60-781 Poznań, Poland.
Jagodzinski
Paweł P
PP
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D010456:Peptides, Cyclic / Q000494:pharmacology*; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology*
C068651:E6 protein, Human papillomavirus type 16; D056572:Histone Deacetylase Inhibitors; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010456:Peptides, Cyclic; D012097:Repressor Proteins; C102351:apicidin; C059731:oncogene protein E7, Human papillomavirus type 16