Vitamin E delta-tocotrienol levels in tumor and pancreatic tissue of mice after oral administration.
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.
Husain
Kazim
K
Department of Gastrointestinal Oncology and Drug Discovery, Moffitt Cancer Center, Department of Oncological Sciences University of South Florida, Tampa, FL 33612, USA.
Francois
Rony A
RA
Hutchinson
Sean Z
SZ
Neuger
Anthony M
AM
Lush
Richard
R
Coppola
Domenico
D
Sebti
Said
S
Malafa
Mokenge P
MP
D000284:Administration, Oral; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006207:Half-Life; D008099:Liver / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000517:prevention & control; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity
D014810:Vitamin E; C082097:tocotrienol, delta