Dietary resveratrol does not delay engraftment, sensitize to vincristine or inhibit growth of high-risk acute lymphoblastic leukemia cells in NOD/SCID mice

• Published in: International journal of oncology Vol. 41; no. 6; pp. 2207 - 2212
• Main Authors: ZUNINO, SUSAN J, STORMS, DAVID H, NEWMAN, JOHN W, PEDERSEN, THERESA L, KEEN, CARL L, DUCORE, JONATHAN M
• Format: Journal Article
• Language: English
• Published: Athens D.A. Spandidos 01-12-2012; Editorial Academy of the International Journal of Oncology; Spandidos Publications UK Ltd
• Subjects: acute lymphoblastic leukemia; Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - metabolism; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Biological and medical sciences; Body Weight - drug effects; Bone marrow; Cancer; Cell cycle; Cell Line, Tumor; Chemotherapy; Diet; dietary resveratrol; Drug dosages; Female; Food; Glucuronides - metabolism; Hematologic and hematopoietic diseases; Humans; Kinases; Laboratories; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical prognosis; Medical sciences; Metabolites; Metastasis; Mice; Mice, Inbred NOD; Mice, SCID; Neoplasm Transplantation; NOD/SCID mice; Pathogens; Patients; Polyphenols; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diet therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Proteins; Rodents; Stilbenes - administration & dosage; Stilbenes - metabolism; Stilbenes - pharmacology; Studies; Sulfates - metabolism; Transcription factors; Tumor Burden - drug effects; Tumors; Vincristine - administration & dosage; Vincristine - pharmacology; Xenograft Model Antitumor Assays; Antineoplastic agent; High risk; Growth; NOD/SCID mouse; Alkaloid; Polyphenol; Cancerology; Lymphoproliferative syndrome; Resveratrol; Acute lymphocytic leukemia; Antimitotic; dietary resveratrol; Nutrition; Malignant hemopathy; Vincristine; Stilbene derivatives; Feeding; Diet; Phytoalexin; acute lymphoblastic leukemia; Phenols; Engraftment; Inhibitor; NOD/ SCID mice; Cancer
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2012.1650

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.