Role of wild-type p53 in the enhancement of camptothecin cytotoxicity against human prostate tumor cells

Ifeyinwa N. Arah, Kaimei Song, Prem Seth, Kenneth H. Cowan, Birandra K. Sinha

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The role of wild-type human p53 protein in enhancing camptothecin cytotoxicity was examine by infecting human prostate PC3 cells with adenovirus expressing human wild-type p53 gene (Adwtp53). The prostate PC3 cells are null for p53 gene. Infection induced the synthesis of both wtp53, and WAF1 (p21) proteins, resulting in growth arrest of PC3 cells. In the presence of camptothecin, an inhibitor of topoisomerase 1, significant increases in both p53 and p21 proteins were detected in Adwtp53-infected PC3 cells. While Adwtp53 and camptothecin, as single agents, caused apoptosis and cell death, combinations of camptothecin and Adwtp53 were better in inducing apoptosis and cell death in PC3 cells. In contrast, cisplatin neither stabilized p53 and p21 proteins nor enhanced DNA fragmentation when combined with Adwtp53 in PC3 cells, indicating specificity for camptothecin. These observations suggest that introduction of wild-type p53 gene with topoisomerase I inhibitors may offer a clinical advantage for the treatment of prostate tumors containing mut53 or null for p53 gene.

Original languageEnglish (US)
Pages (from-to)1845-1849
Number of pages5
JournalAnticancer Research
Volume18
Issue number3 A
StatePublished - May 1 1998

Fingerprint

Camptothecin
p53 Genes
Prostate
Topoisomerase I Inhibitors
Neoplasms
Proteins
Cell Death
Apoptosis
Human Adenoviruses
Null Lymphocytes
DNA Fragmentation
Cisplatin
Growth
Infection

Keywords

  • Adenovirus
  • Apoptosis prostate tumor
  • Camptothecin
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Role of wild-type p53 in the enhancement of camptothecin cytotoxicity against human prostate tumor cells. / Arah, Ifeyinwa N.; Song, Kaimei; Seth, Prem; Cowan, Kenneth H.; Sinha, Birandra K.

In: Anticancer Research, Vol. 18, No. 3 A, 01.05.1998, p. 1845-1849.

Research output: Contribution to journalArticle

Arah, Ifeyinwa N. ; Song, Kaimei ; Seth, Prem ; Cowan, Kenneth H. ; Sinha, Birandra K. / Role of wild-type p53 in the enhancement of camptothecin cytotoxicity against human prostate tumor cells. In: Anticancer Research. 1998 ; Vol. 18, No. 3 A. pp. 1845-1849.
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