Background: Epstein Barr virus-associated lymphoproliferative disease is an increasing complication in patients with immunosuppressive conditions. Although the current therapies for this disorder are effective, they are also associated with significant toxicity. In an attempt to identify newer therapeutic agents, this study investigated the effects of Resveratrol, a naturally occurring polyphenolic compound, on the EBV transformation of human B cells. Methodology/Principal Findings: This study demonstrates that resveratrol prevents EBV transformation in human B cells. These effects are mediated by specific cytotoxic activities of resveratrol against EBV-infected B cells that are associated with the downregulation of the anti-apoptotic proteins Mcl-1 and survivin. This occurs as a consequence of the inhibition of EBV-induced NFkB and STAT-3 signaling pathways and a resveratrol-induced decrease in the expression of the oncogenic viral product LMP1 in EBV-infected B cells. In addition, resveratrol decreased the expression of miR-155 and miR-34a in EBV-infected B cells, blocked the expression of the anti-apoptotic viral gene BHRF1, and thus interrupted events that are critical for EBV transformation and the survival of EBV-transformed cells. Conclusions/Significance: These results suggest that resveratrol may therefore be a potentially effective therapeutic alternative for preventing EBV-associated lymphoproliferative diseases in immune compromised patients.
机构:
F Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Allantaz, Florence
;
Cheng, Donavan T.
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Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ USAF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Cheng, Donavan T.
;
Bergauer, Tobias
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机构:
F Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Bergauer, Tobias
;
Ravindran, Palanikumar
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h-index: 0
机构:
Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ USAF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Ravindran, Palanikumar
;
Rossier, Michel F.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Hosp Geneva, Dept Genet & Lab Med, Geneva, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Rossier, Michel F.
;
Ebeling, Martin
论文数: 0引用数: 0
h-index: 0
机构:
F Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Ebeling, Martin
;
Badi, Laura
论文数: 0引用数: 0
h-index: 0
机构:
F Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Badi, Laura
;
Reis, Bernhard
论文数: 0引用数: 0
h-index: 0
机构:
F Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Reis, Bernhard
;
Bitter, Hans
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h-index: 0
机构:
Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ USAF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Bitter, Hans
;
D'Asaro, Matilde
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h-index: 0
机构:
Univ Hosp Geneva, Dept Genet & Lab Med, Geneva, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
D'Asaro, Matilde
;
Chiappe, Alberto
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h-index: 0
机构:
Univ Hosp Geneva, Dept Genet & Lab Med, Geneva, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Chiappe, Alberto
;
Sridhar, Sriram
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机构:
Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ USAF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Sridhar, Sriram
;
Pacheco, Gonzalo Duran
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h-index: 0
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F Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Pacheco, Gonzalo Duran
;
Burczynski, Michael E.
论文数: 0引用数: 0
h-index: 0
机构:
Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ USAF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Burczynski, Michael E.
;
Hochstrasser, Denis
论文数: 0引用数: 0
h-index: 0
机构:
Univ Hosp Geneva, Dept Genet & Lab Med, Geneva, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Hochstrasser, Denis
;
Vonderscher, Jacky
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Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ USAF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Vonderscher, Jacky
;
Matthes, Thomas
论文数: 0引用数: 0
h-index: 0
机构:
Univ Hosp Geneva, Hematol Serv, Geneva, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
机构:
Harvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USAHarvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA
Baur, Joseph A.
;
Sinclair, David A.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USAHarvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA
机构:
Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA
Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA
VA Med Ctr, Ann Arbor, MI USAUniv Leicester, Dept Canc Studies & Mol Med, LRI,RKCSB, Canc Biomarkers & Prevent Grp, Leicester LE2 7LX, Leics, England
机构:
Sao Paulo State Univ UNESP, Botucatu Sch Med, Dept Pathol, BR-18618000 Botucatu, SP, BrazilSao Paulo State Univ UNESP, Botucatu Sch Med, Dept Pathol, BR-18618000 Botucatu, SP, Brazil
de Oliveira, Deilson Elgui
;
Ballon, Gianna
论文数: 0引用数: 0
h-index: 0
机构:
Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USASao Paulo State Univ UNESP, Botucatu Sch Med, Dept Pathol, BR-18618000 Botucatu, SP, Brazil
Ballon, Gianna
;
Cesarman, Ethel
论文数: 0引用数: 0
h-index: 0
机构:
Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USASao Paulo State Univ UNESP, Botucatu Sch Med, Dept Pathol, BR-18618000 Botucatu, SP, Brazil
机构:
F Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Allantaz, Florence
;
Cheng, Donavan T.
论文数: 0引用数: 0
h-index: 0
机构:
Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ USAF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Cheng, Donavan T.
;
Bergauer, Tobias
论文数: 0引用数: 0
h-index: 0
机构:
F Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Bergauer, Tobias
;
Ravindran, Palanikumar
论文数: 0引用数: 0
h-index: 0
机构:
Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ USAF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Ravindran, Palanikumar
;
Rossier, Michel F.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Hosp Geneva, Dept Genet & Lab Med, Geneva, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Rossier, Michel F.
;
Ebeling, Martin
论文数: 0引用数: 0
h-index: 0
机构:
F Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Ebeling, Martin
;
Badi, Laura
论文数: 0引用数: 0
h-index: 0
机构:
F Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Badi, Laura
;
Reis, Bernhard
论文数: 0引用数: 0
h-index: 0
机构:
F Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Reis, Bernhard
;
Bitter, Hans
论文数: 0引用数: 0
h-index: 0
机构:
Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ USAF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Bitter, Hans
;
D'Asaro, Matilde
论文数: 0引用数: 0
h-index: 0
机构:
Univ Hosp Geneva, Dept Genet & Lab Med, Geneva, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
D'Asaro, Matilde
;
Chiappe, Alberto
论文数: 0引用数: 0
h-index: 0
机构:
Univ Hosp Geneva, Dept Genet & Lab Med, Geneva, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Chiappe, Alberto
;
Sridhar, Sriram
论文数: 0引用数: 0
h-index: 0
机构:
Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ USAF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Sridhar, Sriram
;
Pacheco, Gonzalo Duran
论文数: 0引用数: 0
h-index: 0
机构:
F Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Pacheco, Gonzalo Duran
;
Burczynski, Michael E.
论文数: 0引用数: 0
h-index: 0
机构:
Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ USAF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Burczynski, Michael E.
;
Hochstrasser, Denis
论文数: 0引用数: 0
h-index: 0
机构:
Univ Hosp Geneva, Dept Genet & Lab Med, Geneva, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Hochstrasser, Denis
;
Vonderscher, Jacky
论文数: 0引用数: 0
h-index: 0
机构:
Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ USAF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
Vonderscher, Jacky
;
Matthes, Thomas
论文数: 0引用数: 0
h-index: 0
机构:
Univ Hosp Geneva, Hematol Serv, Geneva, SwitzerlandF Hoffmann La Roche Ltd, Pharma Res & Early Dev, Translat Res Sci, Basel, Switzerland
机构:
Harvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USAHarvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA
Baur, Joseph A.
;
Sinclair, David A.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USAHarvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA
机构:
Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA
Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA
VA Med Ctr, Ann Arbor, MI USAUniv Leicester, Dept Canc Studies & Mol Med, LRI,RKCSB, Canc Biomarkers & Prevent Grp, Leicester LE2 7LX, Leics, England
机构:
Sao Paulo State Univ UNESP, Botucatu Sch Med, Dept Pathol, BR-18618000 Botucatu, SP, BrazilSao Paulo State Univ UNESP, Botucatu Sch Med, Dept Pathol, BR-18618000 Botucatu, SP, Brazil
de Oliveira, Deilson Elgui
;
Ballon, Gianna
论文数: 0引用数: 0
h-index: 0
机构:
Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USASao Paulo State Univ UNESP, Botucatu Sch Med, Dept Pathol, BR-18618000 Botucatu, SP, Brazil
Ballon, Gianna
;
Cesarman, Ethel
论文数: 0引用数: 0
h-index: 0
机构:
Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USASao Paulo State Univ UNESP, Botucatu Sch Med, Dept Pathol, BR-18618000 Botucatu, SP, Brazil