Resveratrol Induces Apoptosis in an Activated B-Cell Lymphoma Line OCI-LY3

Abstract

RATIONALE: Keeping with data showing the polyphenolic compound resveratrol has proven anti-tumor properties in several distinct cell lines, we examined efficacy in a subset of diffuse large B cell lymphoma (DLBCL), activated B-cell (ABC) lymphoma.METHODS: OCI-LY3 cells were cultured and prepared for flow cytometry, western blot analysis, electrophoretic mobility shift assay (EMSA) analysis and siRNA experiments.RESULTS: Resveratrol, which has been previously shown to induce 5% cell death in normal human lymphocytes at a concentration of 100μM, was shown to induce substantial (>70%) cell death in OCI-LY3 cells. We have found that the mechanism underlying cell death involves the downregulation of the AKT/MEK/ERK pathway, as well as the anti-apoptotic protein Bcl-xL. The downregulation of Bcl-xL occurs despite the upregulation of NF-κB, an anti-apoptotic transcription factor which (i) is a major part of the unique ABC gene signature and (ii) binds specifically to κB elements in the Bcl-xL promoter and is thought to cause upregulation of the Bcl-xL gene.CONCLUSIONS: Resveratrol induces apoptosis in the ABC DLBCL cell line OCI-LY3 in a dose-dependent manner involving the inactivation of the AKT/MEK/ERK pathway and reduction in Bcl-xL protein, despite the resveratrol-induced upregulation of NF-κB. Thus, we show a mechanism in which resveratrol plays an anti-cancerous role and present data that resveratrol is a potent inducer of cell death in a subset of lymphoma in which traditional chemotherapy remains fairly ineffective. RATIONALE: Keeping with data showing the polyphenolic compound resveratrol has proven anti-tumor properties in several distinct cell lines, we examined efficacy in a subset of diffuse large B cell lymphoma (DLBCL), activated B-cell (ABC) lymphoma. METHODS: OCI-LY3 cells were cultured and prepared for flow cytometry, western blot analysis, electrophoretic mobility shift assay (EMSA) analysis and siRNA experiments. RESULTS: Resveratrol, which has been previously shown to induce 5% cell death in normal human lymphocytes at a concentration of 100μM, was shown to induce substantial (>70%) cell death in OCI-LY3 cells. We have found that the mechanism underlying cell death involves the downregulation of the AKT/MEK/ERK pathway, as well as the anti-apoptotic protein Bcl-xL. The downregulation of Bcl-xL occurs despite the upregulation of NF-κB, an anti-apoptotic transcription factor which (i) is a major part of the unique ABC gene signature and (ii) binds specifically to κB elements in the Bcl-xL promoter and is thought to cause upregulation of the Bcl-xL gene. CONCLUSIONS: Resveratrol induces apoptosis in the ABC DLBCL cell line OCI-LY3 in a dose-dependent manner involving the inactivation of the AKT/MEK/ERK pathway and reduction in Bcl-xL protein, despite the resveratrol-induced upregulation of NF-κB. Thus, we show a mechanism in which resveratrol plays an anti-cancerous role and present data that resveratrol is a potent inducer of cell death in a subset of lymphoma in which traditional chemotherapy remains fairly ineffective.