Resveratrol induces apoptosis in transformed follicular lymphoma OCI-LY8 cells: evidence for a novel mechanism involving inhibition of BCL6 signaling.
Resveratrol is a polyphenolic compound that exhibits anti-proliferative and anti-inflammatory activities. BCL6, a transcriptional repressor frequently translocated in lymphomas, including diffuse large B-cell lymphoma (DLBCL) and transformed follicular lymphoma (FL), regulates germinal center B-cell differentiation. We report herein that resveratrol treatment of human LY8 follicular lymphoma cells leads to an accumulation of LY8 cell in G0/G1 phase and apoptosis. Resveratrol decreased the expression of BCL6 protein, concomitant with the increased expression of several BCL6 regulated gene products, including p27, p53 and CD69. In addition, resveratrol reduces Myc expression in LY8 cells. These results demonstrate for the first time that resveratrol inhibits a BCL6-linked pathway and suggest that loss of BCL6 expression may represent a key event underlying the anti-proliferative activities of resveratrol on LY8 cells. The use of resveratrol to treat aggressive lymphomas with BCL6 and/or MYC translocations may prove useful as an effective therapy.
Faber
Anthony C
AC
Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
Chiles
Thomas C
TC
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016259:Genes, myc / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D051560:Proto-Oncogene Proteins c-bcl-6; D013267:Stilbenes; C413374:p27 antigen; D020929:Mitogen-Activated Protein Kinase Kinases; D000077185:Resveratrol