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

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 delta-tocotrienol in mice because of its anti-tumor activity against pancreatic cancer. Following a single oral administration of delta-tocotrienol at 100 mg/kg, the peak plasma concentration (C(max)) was 57 +/- 5 micromol/l, the time required to reach peak plasma concentration (T(max)) was 2 h and plasma half-life (t(1/2)) was 3.5 h. The delta-tocotrienol was cleared from plasma and liver within 24 h, but delayed from the pancreas. When mice were fed delta-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 delta-tocotrienol which inhibited tumor growth by 80% in our previous studies. Interestingly, delta-tocotrienol was 10-fold more concentrated in the pancreas than in the tumor. We observed no toxicity due to delta-tocotrienol as mice gained normal weight with no histopathological changes in tissues. Our data suggest that bioactive levels of delta-tocotrienol can be achieved in the pancreas following oral administration and supports its clinical investigation in pancreatic cancer.

• Authors: Kazim Husain, Rony A Francois, Sean Z Hutchinson, Anthony M Neuger, Richard Lush, Domenico Coppola, Said Sebti, Mokenge P Malafa
• Journal: Pharmacology (Pharmacology) Vol. 83 Issue 3 Pg. 157-63 ( 2009) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 19142032 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: 2009 S. Karger AG, Basel.

Chemical References

• Vitamin E
• tocotrienol, delta

Topics

• Administration, Oral
• Animals
• Cell Line, Tumor
• Female
• Half-Life
• Liver (metabolism)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Pancreas (metabolism)
• Pancreatic Neoplasms (metabolism, prevention & control)
• Tissue Distribution
• Transplantation, Heterologous
• Vitamin E (administration & dosage, analogs & derivatives, blood, pharmacokinetics, toxicity)