DTCM-Glutarimide Hinders Growth of Childhood Leukemia Cells but Fails to Improve the Efficacy of Commonly Used Chemotherapeutic Agents

Background: Despite the progressive improvement in current treatment, one fourth of children with acute lymphoblastic leukemia (ALL) still relapse and endure dismal prognosis. In the present study, we introduce more evidence of the antiproliferative effects of 3-[(dodecylthiocarbonyl)-methyl]- glutarimide (DTCM-g), a novel synthetic derivative of 9-methylstreptimidone, on four childhood ALL derived cell lines. Methods: REH, NALM-6, MOLT4 and Jurkat cell lines were treated with varied doses of DTCM-g (2.5 to 20ug/mL) and analyzed in terms of growth (Resazurin reduction), apoptosis (caspase-activation) and cell cycle dynamics. The impact on drug interactions in simultaneous treatments with vincristine, methotrexate and 6-mercaptopurine was also investigated. Results: Our results showed statistically significant reductions in growth in dose- and time-dependent manner, as compared with untreated control cells. In parallel, DTCM-g treatment mediated a significant increase in apoptosis and arrest at the G1 stage of the cell cycle. Alternatively, DTCM-g failed to potentiate the cytotoxicity of the commonly used drugs in 3 of the ALL cell lines studied. Conclusion: Together the data reinforce the anticancer potential of DTCM-g although its applicability in polychemotherapeutic treatments deserves further investigation.