Arsenic trioxide induces apoptosis of HPV16 DNA-immortalized human cervical epithelial cells and selectively inhibits viral gene expression.
Arsenic trioxide (As2O3), a major ingredient of arsenic compounds in traditional Chinese medicine, exhibits anti-acute promyelocytic leukemic activity. Considering that over 80% of human malignant tumors derive from epithelial cells, we studied the effect of As2O3 on HPV 16 DNA-immortalized human cervical epithelial cells (HCE16/3 cells) in vitro. As2O3 reduced HCE16/3 cell survival, induced apoptosis at a low concentration and selectively inhibited expression of viral early genes. This effect was evidenced by a reduction of cell viability in the MTT assay, G1 arrest and significant apoptosis upon flow-cytometric analysis, presence of apoptotic bodies, formation of DNA ladders upon gel electrophoresis and inhibition of viral early gene expression by RT-PCR and Western blot. There was a good correlation between cell apoptosis and viral early gene inhibition after As2O3 treatment, suggesting that induction of apoptosis of HCE16/3 cells by As2O3 treatment might be associated with down-regulation of viral oncogene expression. In conclusion, our findings indicate that As2O3 induces apoptosis of HCE16/3 cells, which may provide a new approach for treating HPV-associated tumors.
Zheng
J
J
Department of Cell Biology, Cancer Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China. zhenjie@jlonline.com
Deng
Y P
YP
Lin
C
C
Fu
M
M
Xiao
P G
PG
Wu
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002461:Cell Line, Transformed / Q000187:drug effects / Q000821:virology; D002472:Cell Transformation, Viral; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects* / Q000821:virology; D004249:DNA Damage; D053938:DNA Fragmentation; D004279:DNA, Viral / Q000235:genetics*; D004847:Epithelial Cells / Q000187:drug effects / Q000821:virology; D005260:Female; D016193:G1 Phase; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D006801:Humans; D008516:Medicine, Chinese Traditional; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics; D010087:Oxides / Q000494:pharmacology*; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology; D050725:Papillomavirus E7 Proteins
D000970:Antineoplastic Agents; D001152:Arsenicals; D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D010087:Oxides; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D000077237:Arsenic Trioxide