Exp Mol Med.  2002 May;34(2):159-166.

HPV E6 antisense induces apoptosis in CaSki cells via suppression of E6 splicing

• Cho CW
• Poo H
• Cho YS
• Cho MC
• Lee KA
• Lee SJ
• Park SN
• Kim IK
• Jung YK
• Choe YK
• Yeom YI
• Choe IS
• Yoon DY

Abstract

Cervical cancer is known to be highly associated with viral oncogene E6 and E7 of human papilloma virus. Down-regulation of oncogene expression by antisense-based gene therapy has been extensively studied. To investigate the effect of HPV 16 E6 antisense nucleic acid (AS) on cervical cancer cells, human cervical cancer cell lines, CaSki and SiHa cells harboring HPV 16 genome were transfected with plasmid containing E6(AS). The decreased viability and the apoptotic morphology were observed in E6(AS)-transfected cervical cancer cell lines. By 6 h after transfection, inhibition of E6 splicing, rapid upregulations of p53 and a p53-responsive protein, GADD45, were displayed in E6(AS)-transfected CaSki cells. Furthermore, E6(AS) induced loss of mitochondrial transmembrane potential, release of mitochondrial cytochrome c into the cytoplasm, and subsequent activation of caspase-9 and caspase-3. These results indicate that HPV 16 E6(AS) induces apoptosis in CaSki cells via upregulation of p53 and release of cytochrome c into cytoplasm, consequently activating procaspase-9 and procaspase-3.

MeSH Terms

*Apoptosis
Caspases/metabolism
Cervix Neoplasms/genetics/therapy/*virology
Cytochrome c Group/metabolism
*DNA, Antisense
*DNA, Viral/physiology
Female
Human
Membrane Potentials
Mitochondria/metabolism
Oncogene Proteins, Viral/*genetics
Papillomavirus, Human/genetics/*physiology
Protein p53/metabolism
*RNA Splicing
Tumor Cells, Cultured
Up-Regulation