Adenovirus-mediated p21((WAF1/SDII/CIP1)) gene transfer induces apoptosis of human cervical cancer cell lines

Yeou Ping Tsao, Shyh Jer Huang, Junn Liang Chang, Jer Tsong Hsieh, Rey Chen Pong, Show Li Chen

Research output: Contribution to journalArticle

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Abstract

921((WAF1/SDII/CIP1)) (p21) arrests cell growth by inhibiting cyclin- depend kinases. To explore the potential of using p21 for the gene therapy of cervical cancer, we infected human papillomavirus (HPV)-positive cervical cancer cells (HeLa, SiHa, and Z172) and HPV-negative cervical cancer cells (C33A) with recombinant adenovirus encoding p21 cDNA. The results revealed that effective inhibition of cell growth could be achieved by sense p21 adenovirus but not antisense p21 adenovirus infection and occurred through apoptosis as measured by DNA fragmentation and chromatin condensation. Apoptosis was also observed in xenografts of human cervical cancer cells infected with sense p21 adenovirus, as confirmed by in situ terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL). The apoptosis was not prevented by overexpression of the bcl-2 transgene. To sum up, the apoptotic effect suggests that p21 should be a tumoricidal agent instead of a tumoristatic agent in preventing cervical cancers. In addition, our report substantiates the combination of the high efficiency of adenovirus vector-mediated gene delivery and the apoptotic effect of p21.

Original languageEnglish (US)
Pages (from-to)4983-4990
Number of pages8
JournalJournal of Virology
Volume73
Issue number6
StatePublished - 1999

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uterine cervical neoplasms
Adenoviridae
gene transfer
Uterine Cervical Neoplasms
apoptosis
cell lines
Apoptosis
Cell Line
Papillomaviridae
Genes
cell growth
Adenoviridae Infections
Cyclins
gene therapy
DNA Nucleotidylexotransferase
DNA fragmentation
In Situ Nick-End Labeling
cyclins
DNA Fragmentation
biotin

ASJC Scopus subject areas

  • Immunology

Cite this

Tsao, Y. P., Huang, S. J., Chang, J. L., Hsieh, J. T., Pong, R. C., & Chen, S. L. (1999). Adenovirus-mediated p21((WAF1/SDII/CIP1)) gene transfer induces apoptosis of human cervical cancer cell lines. Journal of Virology, 73(6), 4983-4990.

Adenovirus-mediated p21((WAF1/SDII/CIP1)) gene transfer induces apoptosis of human cervical cancer cell lines. / Tsao, Yeou Ping; Huang, Shyh Jer; Chang, Junn Liang; Hsieh, Jer Tsong; Pong, Rey Chen; Chen, Show Li.

In: Journal of Virology, Vol. 73, No. 6, 1999, p. 4983-4990.

Research output: Contribution to journalArticle

Tsao, YP, Huang, SJ, Chang, JL, Hsieh, JT, Pong, RC & Chen, SL 1999, 'Adenovirus-mediated p21((WAF1/SDII/CIP1)) gene transfer induces apoptosis of human cervical cancer cell lines', Journal of Virology, vol. 73, no. 6, pp. 4983-4990.
Tsao, Yeou Ping ; Huang, Shyh Jer ; Chang, Junn Liang ; Hsieh, Jer Tsong ; Pong, Rey Chen ; Chen, Show Li. / Adenovirus-mediated p21((WAF1/SDII/CIP1)) gene transfer induces apoptosis of human cervical cancer cell lines. In: Journal of Virology. 1999 ; Vol. 73, No. 6. pp. 4983-4990.
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AU - Pong, Rey Chen

AU - Chen, Show Li

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N2 - 921((WAF1/SDII/CIP1)) (p21) arrests cell growth by inhibiting cyclin- depend kinases. To explore the potential of using p21 for the gene therapy of cervical cancer, we infected human papillomavirus (HPV)-positive cervical cancer cells (HeLa, SiHa, and Z172) and HPV-negative cervical cancer cells (C33A) with recombinant adenovirus encoding p21 cDNA. The results revealed that effective inhibition of cell growth could be achieved by sense p21 adenovirus but not antisense p21 adenovirus infection and occurred through apoptosis as measured by DNA fragmentation and chromatin condensation. Apoptosis was also observed in xenografts of human cervical cancer cells infected with sense p21 adenovirus, as confirmed by in situ terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL). The apoptosis was not prevented by overexpression of the bcl-2 transgene. To sum up, the apoptotic effect suggests that p21 should be a tumoricidal agent instead of a tumoristatic agent in preventing cervical cancers. In addition, our report substantiates the combination of the high efficiency of adenovirus vector-mediated gene delivery and the apoptotic effect of p21.

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