An HIV protease inhibitor, ritonavir targets the nuclear factor-kappaB and inhibits the tumor growth and infiltration of EBV-positive lymphoblastoid B cells
✍ Scribed by Md. Zahidunnabi Dewan; Mariko Tomita; Harutaka Katano; Norio Yamamoto; Sunjida Ahmed; Michiko Yamamoto; Tetsutaro Sata; Naoki Mori; Naoki Yamamoto
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- French
- Weight
- 411 KB
- Volume
- 124
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Epstein‐Barr Virus (EBV)‐associated immunoblastic lymphoma occurs in immunocompromised patients such as those with AIDS or transplant recipients after primary EBV infection or reactivation of a preexisting latent EBV infection. In the present study, we evaluated the effect of ritonavir, an HIV protease inhibitor, on EBV‐positive lymphoblastoid B cells in vitro and in mice model. We found that it induced cell‐cycle arrest at G~1~‐phase and apoptosis through down‐regulation of cell‐cycle gene cyclin D2 and antiapoptotic gene survivin. Furthermore, ritonavir suppressed transcriptional activation of NF‐κB in these cells. Ritonavir efficiently prevented growth and infiltration of lymphoma cells in various organs of NOD/SCID/γc^null^ mice at the same dose used for treatment of patients with AIDS. Our results indicate that ritonavir targets NF‐κB activated in tumor cells and shows anti‐tumor effects. These data also suggest that this compound may have promise for treatment or prevention of EBV‐associated lymphoproliferative diseases that occur in immunocompromised patients. © 2008 Wiley‐Liss, Inc.