HPV E6 antisense induces apoptosis in CaSki cells via suppression of E6 splicing.
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.
Cho
Cheong Weon
CW
Division of Life Sciences, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Taejon.
Poo
Haryoung
H
Cho
Young Sik
YS
Cho
Min Chul
MC
Lee
Kyung Ae
KA
Lee
Shin Je
SJ
Park
Sue Nie
SN
Kim
In Ki
IK
Jung
Yong Keun
YK
Choe
Yong Kyung
YK
Yeom
Young I I
YI
Choe
In Seong
IS
Yoon
Do Young
DY
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D016373:DNA, Antisense; D004279:DNA, Viral / Q000502:physiology; D005260:Female; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology*; D012326:RNA Splicing; D012097:Repressor Proteins; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000628:therapy / Q000821:virology*
D003574:Cytochrome c Group; D016373:DNA, Antisense; D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D020169:Caspases