title: Dietary resveratrol does not delay engraftment, sensitize to vincristine             or inhibit growth of high-risk acute lymphoblastic leukemia cells in NOD/SCID             mice.
abstract: Acute lymphoblastic leukemia (ALL) with translocation t(4;11) is a high-risk leukemia found in 60-85% of infants with ALL and is often refractory to conventional chemotherapeutics after relapse. To evaluate the efficacy of dietary resveratrol in vivo, 5-week-old NOD.CB17-Prkdcscid/J mice were fed a control diet or a diet containing 0.2% w/w resveratrol. After 3 weeks of dietary treatment, mice were engrafted with the human t(4;11) ALL line SEM by tail vein injection. Engraftment was monitored by evaluating the presence of human CD19+ cells in peripheral blood using flow cytometry. Relative to control diet, dietary resveratrol did not delay the engraftment of the leukemia cells. To determine if dietary resveratrol could increase efficacy of a chemotherapeutic agent, vincristine was injected intraperitoneally into leukemic mice fed the control or supplemented diet. Survival curves and monitoring the percentage of human leukemia cells in peripheral blood showed that resveratrol did not inhibit leukemia cell growth or influence the activity of vincristine. Mass spectrometric analysis of mouse serum revealed that the majority of resveratrol was present as glucuronidated and sulfated metabolites. These data do not support the concept that dietary resveratrol has potential as a preventative agent against the growth of high-risk t(4;11) ALL.
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA 95616, USA. susan.zunino@ars.usda.gov
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Zunino
authors.forename: David H
authors.initials: DH
authors.lastname: Storms
authors.forename: John W
authors.initials: JW
authors.lastname: Newman
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Pedersen
authors.forename: Carl L
authors.initials: CL
authors.lastname: Keen
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Ducore
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D004032:Diet; D005260:Female; D020719:Glucuronides / Q000378:metabolism; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000178:diet therapy / Q000401:mortality / Q000473:pathology*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D013431:Sulfates / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D014750:Vincristine / Q000008:administration & dosage / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020719:Glucuronides; D013267:Stilbenes; D013431:Sulfates; D014750:Vincristine; D000077185:Resveratrol