Sodium arsenite suppresses human papillomavirus-16 E6 gene and enhances apoptosis in E6-transfected human lymphoblastoid cells.
The p53 tumor suppressor pathway is disrupted by human papillomavirus (HPV) in most cervical cancer cells. The E6 proteins, which could mediate p53 degradation, are related to cellular immortalization, transformation, and tumor formation. In order to study the E6 abrogated p53 function in stress, we transfected HPV-16 E6 gene to TK6 cells in this study. Here we showed that HPV-16 E6 mRNA levels decreased in a dose dependent manner after sodium arsenite (SA) treatment, but not after X-irradiation. P53, p21, and MDM2 were induced in E6-transfected TK6 cells, as well as in parental TK6 cells after arsenite treatment. But the above proteins were only induced in TK6 cells after X-irradiation. It indicated that arsenite, but not X-ray, could suppress the transcription of E6 gene and therefore activate the p53 tumor suppressor pathway in TK6-E6 cells. After arsenite treatment, TK6-E6 cells showed more sub-G1 apoptosis, activated caspase-3/CPP32 fragment, DNA ladder, and less viability than parental TK6 cells, indicating that arsenite enhanced apoptosis in E6-transfected TK6 cells. In contrast, after X-irradiation, TK6-E6 cells showed less sub-G1 apoptosis and higher viability than parental TK6 cells. Thus, it would be another possible strategy to promote arsenite as another potential candidate for the therapeutic purpose in HPV-positive cancer cells.
Chou
Ruey-Hwang
RH
Department of Life Science, National Tsing-Hua University, HsinChu 30043, Taiwan, Republic of China.
Huang
Haimei
H
D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000494:pharmacology* / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002999:Clone Cells; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000378:metabolism; D011839:Radiation, Ionizing; D012097:Repressor Proteins; D017670:Sodium Compounds / Q000494:pharmacology* / Q000633:toxicity*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018053:Arsenites; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C068651:E6 protein, Human papillomavirus type 16; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D017670:Sodium Compounds; D016159:Tumor Suppressor Protein p53; C017947:sodium arsenite; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2