Leflunomide Reduces Proliferation and Induces Apoptosis in Neuroblastoma Cells In Vitro and In Vivo
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| Authors: | Shunqin Zhu Xiaomin Yan Zhonghuai Xiang Han-Fei Ding Hongjuan Cui |
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| Institution: | 1. State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.; 2. College of Life Science, Southwest University, Chongqing, China.; 3. Cancer Center and Department of Pathology, Georgia Health Sciences University, Augusta, Georgia, United States of America.; Univ of Bradford, United Kingdom, |
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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. |
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