Valproic acid enhances the efficacy of chemotherapy in EBV-positive tumors by increasing lytic viral gene expression.

Valproic acid enhances the efficacy of chemotherapy in EBV-positive tumors by increasing lytic viral gene expression. Research Abstract Details 

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Valproic acid enhances the efficacy of chemotherapy in EBV-positive tumors by increasing lytic viral gene expression. Abstract Text:

Wen-Hai Feng,Shannon C Kenney,

EBV infection in tumor cells is generally restricted to the latent forms of viral infection. Switching the latent form of viral infection into the lytic form may induce tumor cell death. We have previously reported that certain chemotherapy agents can increase the amount of lytic viral gene expression in EBV-positive tumor cells. In this report, we have explored the potential utility of valproic acid (VPA), an anti-seizure drug that also has strong histone deacetylase inhibitory activity, for activating lytic viral gene expression in EBV-positive tumors. Although VPA treatment alone induced only a modest increase in the level of lytic viral gene expression, it strongly enhanced the ability of chemotherapeutic agents to induce lytic EBV gene expression in EBV-positive epithelial and lymphoid cells in vitro. Furthermore, VPA enhanced cell killing in vitro by chemotherapeutic agents in lymphoblastoid cells and gastric cells (AGS) containing wild-type EBV. In contrast, VPA did not enhance the cytotoxicity of chemotherapy in lymphoblastoid cells containing a lytic-defective (BZLF1-knockout) form of EBV or in EBV-negative AGS cells. Finally, we found that the combination of VPA and chemotherapy was significantly more effective in inhibiting EBV-driven lymphoproliferative disease in severe combined immunodeficient mice than chemotherapy alone. These results suggest that VPA could potentiate the efficacy of chemotherapy for EBV-positive tumors in patients.

Valproic acid enhances the efficacy of chemotherapy in EBV-positive tumors by increasing lytic viral gene expression. Publishing Authors By Initials

WH Feng,SC Kenney,

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Valproic acid enhances the efficacy of chemotherapy in EBV-positive tumors by increasing lytic viral gene expression. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Cancer research

VOLUME: 66

Page Numbers: 8762-9

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ISSN: 1538-7445

DAY: 1

MONTH: Sep

YEAR: 2006

Valproic acid enhances the efficacy of chemotherapy in EBV-positive tumors by increasing lytic viral gene expression. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

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Grant and Affiliation Information for Valproic acid enhances the efficacy of chemotherapy in EBV-positive tumors by increasing lytic viral gene expression.

AFFILIATION: Department of Medicine and Microbiology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Country: United States

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MEDLINETA: Cancer Res

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