Ribonucleotide reductase inhibitors enhance cidofovir-induced apoptosis in EBV-positive nasopharyngeal carcinoma xenografts

• Wakisaka, Naohiro

• Yoshizaki, Tomokazu

• Raab-Traub, Nancy

• Pagano, Joseph S.

抄録

金沢大学医学部附属病院耳鼻咽喉科

In nasopharyngeal carcinoma (NPC), Epstein-Barr virus (EBV) infection is mainly latent, and the tumor cells contain episomal viral DNA. We have shown that the acyclic nucleoside phosphonate analog, cidofovir [(S)-1-(3-hydroxy-2- (phosphonylmethoxypropyl)cytosine] (HPMPC), inhibits growth of NPC xenografts in nude mice by causing apoptosis. The ribonucleotide reductase (RR) inhibitors, hydroxyurea and didox (3,4-dihydroxybenzohydroxamic acid), have been demonstrated to inhibit neoplastic growth and are used as antiviral and anticancer agents. Here we show that RR inhibitors enhance the antitumor effect of cidofovir in EBV-transformed epithelial cells. MTT assays indicate that hydroxyurea and didox enhance cidofovir-induced cell toxicity in NPC-KT cells, an EBV-positive epithelial cell line derived from NPC. The effect is due to enhancement of apoptosis through the caspase cascade as shown by pronounced cleavage of poly(ADP-ribose) polymerase. Finally, hydroxyurea strikingly enhanced the cidofovir-induced growth-inhibitory effect on NPC grown in athymic mice. The results suggest that RR inhibitors should enhance the antitumor effect of acyclic nucleoside phosphonate analogs on NPC. © 2005 Wiley-Liss, Inc.

収録刊行物

• International Journal of Cancer

  International Journal of Cancer 116 (4), 640-645, 2005-07-01

  Wiley-Liss

キーワード

• Apoptosis
• Cidofovir
• Epstein-Barr virus
• Hydroxyurea
• Ribonucleotide reductase inhibitor

詳細情報

• CRID: 1050564285901504640
• NII論文ID: 120001140108
• ISSN: 00207136
• Web Site: http://hdl.handle.net/2297/6766
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles