Proteasome inhibitors induce apoptosis and reduce viral replication in primary effusion lymphoma cells

Chiaki Saji, Chizuka Higashi, Yasufumi Niinaka, Koji Yamada, Kohji Noguchi, Masahiro Fujimuro

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by Kaposi's sarcoma-associated herpesvirus (KSHV). This study provides evidence that proteasomal activity is required for both survival of PEL cells stably harboring the KSHV genome and viral replication of KSHV. We evaluated the cytotoxic effects of proteasome inhibitors on PEL cells. The proteasome inhibitors MG132, lactacystin, and proteasome inhibitor I dramatically inhibited cell proliferation and induced apoptosis of PEL cells through the accumulation of p21 and p27. Furthermore, proteasome inhibitors induced the stabilization of NF-κB inhibitory molecule (IκBα) and suppressed the transcriptional activity of NF-κB in PEL cells. The NF-κB specific inhibitor BAY11-7082 also induced apoptosis in PEL cells. The constitutive activation of NF-κB signaling is essential for the survival and growth of B cell lymphoma cells, including PEL cells. NF-κB signaling is upregulated by proteasome-dependent degradation of IκBα. The suppression of NF-κB signaling by proteasome inhibitors may contribute to the induction of apoptosis in PEL cells. In addition, proteasome activity is required for KSHV replication in KSHV latently infected PEL cells. MG132 reduced the production of progeny virus from PEL cells at low concentrations, which do not affect PEL cell growth. These findings suggest that proteasome inhibitors may represent a novel strategy for the treatment of KSHV infection and KSHV-associated lymphomas.

Original languageEnglish
Pages (from-to)573-578
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume415
Issue number4
DOIs
Publication statusPublished - 2011 Dec 2

Fingerprint

Primary Effusion Lymphoma
Proteasome Inhibitors
Human Herpesvirus 8
Apoptosis
Proteasome Endopeptidase Complex
Molecules
Cell proliferation
Cell growth
Viruses
Stabilization
Genes
Chemical activation
Cells
Degradation
Herpesviridae Infections
Viral Genome
B-Cell Lymphoma
Growth
Lymphoma

Keywords

  • Apoptosis
  • KSHV
  • Lytic replication
  • NF-κB
  • Primary effusion lymphoma
  • Proteasome

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Proteasome inhibitors induce apoptosis and reduce viral replication in primary effusion lymphoma cells. / Saji, Chiaki; Higashi, Chizuka; Niinaka, Yasufumi; Yamada, Koji; Noguchi, Kohji; Fujimuro, Masahiro.

In: Biochemical and Biophysical Research Communications, Vol. 415, No. 4, 02.12.2011, p. 573-578.

Research output: Contribution to journalArticle

Saji, Chiaki ; Higashi, Chizuka ; Niinaka, Yasufumi ; Yamada, Koji ; Noguchi, Kohji ; Fujimuro, Masahiro. / Proteasome inhibitors induce apoptosis and reduce viral replication in primary effusion lymphoma cells. In: Biochemical and Biophysical Research Communications. 2011 ; Vol. 415, No. 4. pp. 573-578.
@article{653eb8d1f6be42da80b48c28d17f14d8,
title = "Proteasome inhibitors induce apoptosis and reduce viral replication in primary effusion lymphoma cells",
abstract = "Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by Kaposi's sarcoma-associated herpesvirus (KSHV). This study provides evidence that proteasomal activity is required for both survival of PEL cells stably harboring the KSHV genome and viral replication of KSHV. We evaluated the cytotoxic effects of proteasome inhibitors on PEL cells. The proteasome inhibitors MG132, lactacystin, and proteasome inhibitor I dramatically inhibited cell proliferation and induced apoptosis of PEL cells through the accumulation of p21 and p27. Furthermore, proteasome inhibitors induced the stabilization of NF-κB inhibitory molecule (IκBα) and suppressed the transcriptional activity of NF-κB in PEL cells. The NF-κB specific inhibitor BAY11-7082 also induced apoptosis in PEL cells. The constitutive activation of NF-κB signaling is essential for the survival and growth of B cell lymphoma cells, including PEL cells. NF-κB signaling is upregulated by proteasome-dependent degradation of IκBα. The suppression of NF-κB signaling by proteasome inhibitors may contribute to the induction of apoptosis in PEL cells. In addition, proteasome activity is required for KSHV replication in KSHV latently infected PEL cells. MG132 reduced the production of progeny virus from PEL cells at low concentrations, which do not affect PEL cell growth. These findings suggest that proteasome inhibitors may represent a novel strategy for the treatment of KSHV infection and KSHV-associated lymphomas.",
keywords = "Apoptosis, KSHV, Lytic replication, NF-κB, Primary effusion lymphoma, Proteasome",
author = "Chiaki Saji and Chizuka Higashi and Yasufumi Niinaka and Koji Yamada and Kohji Noguchi and Masahiro Fujimuro",
year = "2011",
month = "12",
day = "2",
doi = "10.1016/j.bbrc.2011.10.107",
language = "English",
volume = "415",
pages = "573--578",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - Proteasome inhibitors induce apoptosis and reduce viral replication in primary effusion lymphoma cells

AU - Saji, Chiaki

AU - Higashi, Chizuka

AU - Niinaka, Yasufumi

AU - Yamada, Koji

AU - Noguchi, Kohji

AU - Fujimuro, Masahiro

PY - 2011/12/2

Y1 - 2011/12/2

N2 - Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by Kaposi's sarcoma-associated herpesvirus (KSHV). This study provides evidence that proteasomal activity is required for both survival of PEL cells stably harboring the KSHV genome and viral replication of KSHV. We evaluated the cytotoxic effects of proteasome inhibitors on PEL cells. The proteasome inhibitors MG132, lactacystin, and proteasome inhibitor I dramatically inhibited cell proliferation and induced apoptosis of PEL cells through the accumulation of p21 and p27. Furthermore, proteasome inhibitors induced the stabilization of NF-κB inhibitory molecule (IκBα) and suppressed the transcriptional activity of NF-κB in PEL cells. The NF-κB specific inhibitor BAY11-7082 also induced apoptosis in PEL cells. The constitutive activation of NF-κB signaling is essential for the survival and growth of B cell lymphoma cells, including PEL cells. NF-κB signaling is upregulated by proteasome-dependent degradation of IκBα. The suppression of NF-κB signaling by proteasome inhibitors may contribute to the induction of apoptosis in PEL cells. In addition, proteasome activity is required for KSHV replication in KSHV latently infected PEL cells. MG132 reduced the production of progeny virus from PEL cells at low concentrations, which do not affect PEL cell growth. These findings suggest that proteasome inhibitors may represent a novel strategy for the treatment of KSHV infection and KSHV-associated lymphomas.

AB - Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by Kaposi's sarcoma-associated herpesvirus (KSHV). This study provides evidence that proteasomal activity is required for both survival of PEL cells stably harboring the KSHV genome and viral replication of KSHV. We evaluated the cytotoxic effects of proteasome inhibitors on PEL cells. The proteasome inhibitors MG132, lactacystin, and proteasome inhibitor I dramatically inhibited cell proliferation and induced apoptosis of PEL cells through the accumulation of p21 and p27. Furthermore, proteasome inhibitors induced the stabilization of NF-κB inhibitory molecule (IκBα) and suppressed the transcriptional activity of NF-κB in PEL cells. The NF-κB specific inhibitor BAY11-7082 also induced apoptosis in PEL cells. The constitutive activation of NF-κB signaling is essential for the survival and growth of B cell lymphoma cells, including PEL cells. NF-κB signaling is upregulated by proteasome-dependent degradation of IκBα. The suppression of NF-κB signaling by proteasome inhibitors may contribute to the induction of apoptosis in PEL cells. In addition, proteasome activity is required for KSHV replication in KSHV latently infected PEL cells. MG132 reduced the production of progeny virus from PEL cells at low concentrations, which do not affect PEL cell growth. These findings suggest that proteasome inhibitors may represent a novel strategy for the treatment of KSHV infection and KSHV-associated lymphomas.

KW - Apoptosis

KW - KSHV

KW - Lytic replication

KW - NF-κB

KW - Primary effusion lymphoma

KW - Proteasome

UR - http://www.scopus.com/inward/record.url?scp=84855889019&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855889019&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2011.10.107

DO - 10.1016/j.bbrc.2011.10.107

M3 - Article

C2 - 22074820

AN - SCOPUS:84855889019

VL - 415

SP - 573

EP - 578

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -