Vitamin E δ-tocotrienol levels in tumor and pancreatic tissue of mice after oral administration

Kazim Husain, Rony A. Francois, Sean Z. Hutchinson, Anthony M. Neuger, Richard Lush, Domenico Coppola, Said Sebti, Mokenge P. Malafa

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Tocotrienols are natural vitamin E compounds that are known to have a neuroprotective effect at nanomolar concentration and anti-carcinogenic effect at micromolar concentration. In this report, we investigated the pharmacokinetics, tumor and pancreatic tissue levels, and toxicity of δ-tocotrienol in mice because of its anti-tumor activity against pancreatic cancer. Following a single oral administration of δ-tocotrienol at 100 mg/kg, the peak plasma concentration (Cmax) was 57 ± 5 μmol/l, the time required to reach peak plasma concentration (T max) was 2 h and plasma half-life (t1/2) was 3.5 h. The δ-tocotrienol was cleared from plasma and liver within 24 h, but delayed from the pancreas. When mice were fed δ-tocotrienol for 6 weeks, the concentration in tumor tissue was 41 ± 3.5 nmol/g. This concentration was observed with the oral dose (100 mg/kg) of δ-tocotrienol which inhibited tumor growth by 80% in our previous studies. Interestingly, δ-tocotrienol was 10-fold more concentrated in the pancreas than in the tumor. We observed no toxicity due to δ-tocotrienol as mice gained normal weight with no histopathological changes in tissues. Our data suggest that bioactive levels of δ-tocotrienol can be achieved in the pancreas following oral administration and supports its clinical investigation in pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)157-163
Number of pages7
JournalPharmacology
Volume83
Issue number3
DOIs
StatePublished - Feb 1 2009
Externally publishedYes

Keywords

  • Pancreatic cancer
  • Pharmacokinetics
  • Tissue distribution
  • δ-Tocotrienol
  • δ-Tocotrienol, mice

ASJC Scopus subject areas

  • Pharmacology

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    Husain, K., Francois, R. A., Hutchinson, S. Z., Neuger, A. M., Lush, R., Coppola, D., Sebti, S., & Malafa, M. P. (2009). Vitamin E δ-tocotrienol levels in tumor and pancreatic tissue of mice after oral administration. Pharmacology, 83(3), 157-163. https://doi.org/10.1159/000190792