Title: Oral or parenteral administration of curcumin does not prevent the growth of high-risk t(4;11) acute lymphoblastic leukemia cells engrafted into a NOD/SCID mouse model Authors
Submitted to: International Journal of Oncology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 16, 2012
Publication Date: January 8, 2013
Citation: Zunino, S.J., Storms, D.H., Newman, J.W., Pedersen, T.L., Keen, C.L., Ducore, J.M. 2013. Oral or parenteral administration of curcumin does not prevent the growth of high-risk t(4;11) acute lymphoblastic leukemia cells engrafted into a NOD/SCID mouse model. International Journal of Oncology. 42:741-748. DOI: 10.3892/ijo.2012.1734. Interpretive Summary: Curcumin is a chemical found in the spice turmeric and has shown anti-inflammatory and anti-cancer activities. Curcumin has shown anti-cancer activity against high risk acute lymphoblastic leukemia in a cell culture system. This high risk leukemia is found in about 80% of infants with leukemia and has a very poor outcome. Therefore, we determined whether curcumin was effective in killing high risk leukemia in a mouse model for this disease. Immunodeficient mice were injected with leukemia cells that were established from a patient with this high risk leukemia. Leukemic mice were then treated with curcumin by injection or in a second experiment they were fed curcumin in their chow. The curcumin treated mice were compared to control mice (without treatment) and mice treated with vincristine, a chemotherapeutic agent used in the clinic to treat this disease. Comparisons of the percent of human leukemia cells in mouse blood and survival curves showed that curcumin did not inhibit the the growth of this high risk leukemia. Analysis of curcumin levels in the blood of the curcumin-treated mice showed that curcumin was modified by the additions of sugars and sulfur-containing molecules. These data indicate that injected or dietary curcumin does not have potential as a novel preventive agent against high risk leukemia.
Technical Abstract: The efficacy of orally and parenterally administered curcumin was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) acute lymphoblastic leukemia line SEM. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed, the chemotherapeutic potential was tested by injecting mice intraperitoneally with either curcumin (5 mg/kg body weight) dissolved in dimethylsulfoxide (DMSO) or DMSO alone (control) every other day, or vincristine (0.5 mg/kg body weight) 3 times per week for 4 wk (n = 16 per group). Intraperitoneal curcumin did not inhibit growth of the leukemia. To test the oral efficacy of curcumin, mice were fed a control diet or a diet containing 0.5% w/w curumin three weeks prior to injection of the leukemia cells and throughout the experimental period (n = 16 per group). To determine if dietary curcumin could increase efficacy of a conventional chemotherapeutic agent, vincristine was injected intraperitoneally into leukemic mice fed the different diets. Dietary curcumin did not delay the engraftment or growth of leukemia cells, or sensitize the cells to vincristine. Liquid chromatography- tandem mass spectrometry analyses of mouse sera showed curcumin was rapidly metabolized to glucuronidated and sulfated forms 1 h post-injection, and were the major curcumin metabolites found in the sera of mice fed the curcumin diet. These data indicate that in contrast to findings in in vitro models, orally or parenterally administered curcumin may not have potential as a preventive agent against high risk t(4;11) ALL.