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Public Library of Science, PLoS ONE, 8(8), p. e71555, 2013

DOI: 10.1371/journal.pone.0071555

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Leflunomide Reduces Proliferation and Induces Apoptosis in Neuroblastoma Cells In Vitro and In Vivo

Journal article published in 2013 by Shunqin Zhu, Xiaomin Yan, Zhonghuai Xiang, Han-Fei Ding, Hongjuan Cui
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Leflunomide as an immunosuppressive drug is generally used in the treatment of rheumatoid arthritis. It inhibits DHODH (dihydroorotate dehydrogenase ), which is one of the essential enzymes in the de novo pyrimidine biosynthetic pathway. Here we showed that leflunomide significantly reduced cell proliferation and self-renewal activity. Annexin V-FITC/PI staining assay revealed that leflunomide induced S-phase cell cycle arrest, and promoted cell apoptosis. In vivo xenograft study in SCID mice showed that leflunomide inhibited tumor growth and development. We also observed that DHODH was commonly expressed in neuroblastoma. When treated with leflunomide, the neuroblastoma cell lines BE(2)-C, SK-N-DZ, and SK-N-F1 showed dramatic inhibition of DHODH at mRNA and protein levels. Considering the favorable toxicity profile and the successful clinical experience with leflunomide in rheumatoid arthritis, this drug represents a potential new candidate for targeted therapy in neuroblastoma.