Arsenic trioxide induces apoptosis of HPV16 DNA-immortalized human cervical epithelial cells and selectively inhibits viral gene expression

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Abstract
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. Int. J. Cancer 82:286–292, 1999.