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

Shunqin Zhu, Xiaomin Yan, Zhonghuai Xiang, Hanfei Ding, Hongjuan Cui

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere71555
JournalPloS one
Volume8
Issue number8
DOIs
StatePublished - Aug 9 2013

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leflunomide
rheumatoid arthritis
Neuroblastoma
apoptosis
Apoptosis
immunosuppressive agents
drugs
pyrimidines
in vivo studies
interphase
biochemical pathways
cell proliferation
growth and development
cell lines
cells
toxicity
therapeutics
neoplasms
Rheumatoid Arthritis
mice

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Leflunomide Reduces Proliferation and Induces Apoptosis in Neuroblastoma Cells In Vitro and In Vivo. / Zhu, Shunqin; Yan, Xiaomin; Xiang, Zhonghuai; Ding, Hanfei; Cui, Hongjuan.

In: PloS one, Vol. 8, No. 8, e71555, 09.08.2013.

Research output: Contribution to journalArticle

Zhu, Shunqin ; Yan, Xiaomin ; Xiang, Zhonghuai ; Ding, Hanfei ; Cui, Hongjuan. / Leflunomide Reduces Proliferation and Induces Apoptosis in Neuroblastoma Cells In Vitro and In Vivo. In: PloS one. 2013 ; Vol. 8, No. 8.
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