Biotin deficiency stimulates survival pathways in human lymphoma cells exposed to antineoplastic drugs

Jacob B. Griffin, Janos Zempleni

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Cells may respond to nutrient deficiency or death signals with nuclear translocation of the transcription factor nuclear factor κB (NF-κB), which activates transcription of anti-apoptotic genes. Here we tested the hypothesis that biotin deficiency stimulates NF-κB-dependent survival pathways in human lymphoma cells, enhancing resistance to antineoplastic agents. Lymphoma (Jurkat) cells were cultured in biotin-deficient (0.025 nmol/L) and biotin-supplemented (10 nmol/L) media. If cells were treated with antineoplastic agents (taxol, doxorubicin or vinblastine), nuclear translocation of two NF-κB proteins (p50 and p65) was >25% greater in biotin-deficient compared with biotin-supplemented cells. The transcriptional activities of the following NF-κB-dependent reporter genes were 16-59% greater in biotin-deficient compared with biotin-supplemented cells treated with various antineoplastic agents: (1) reporter expression driven by a TATA box and five NF-κB repeats and (2) reporter expression driven by the regulatory region of the anti-apoptotic Bfl-1 gene. Collectively, these findings are consistent with activation of survival pathways in biotin-deficient lymphoma cells. Finally, cells were treated with antineoplastic agents for 48 h and cell survival was monitored at timed intervals. Biotin deficiency was associated with enhanced survival of cells treated with doxorubicin and vinblastine, but did not affect survival of cells treated with taxol. Collectively, these observations suggest that biotin deficiency may enhance resistance of cancer cells to antineoplastic agents.

Original languageEnglish (US)
Pages (from-to)96-103
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume16
Issue number2
DOIs
StatePublished - Feb 2005

Keywords

  • Antineoplastic agents
  • Biotin
  • Chemotherapy
  • Human
  • Jurkat cells
  • NF-κB
  • Survival

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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