Preferential radiation sensitization of prostate cancer in nude mice by nutraceutical antioxidant gamma-tocotrienol.
Gamma-tocotrienol (GT) is a member of the vitamin E family. Our preliminary studies indicated that it protected mice from lethal irradiation, so we hypothesized that GT might be a radiation sensitizing agent for tumors. To test this, we induced prostate tumors by injecting PC3 cells into nude BALB/c mice. When the tumors were about 5 mm in diameter, mice were injected subcutaneously with 400 mg/kg gamma-tocotrienol and irradiated 24 h later at the site of the tumor with a dose of 12 Gy (60)Cobalt. Tumor size was monitored for 24 days after radiation. Tumor tissues as well as normal tissues like rectum, kidney, and liver were monitored for lipid peroxidation on day 4 and day 24 after radiation. The results indicated that the size of the tumors was reduced by almost 40%, but only in GT-treated and irradiated mice. In unstimulated and Fe-stimulated lipid peroxidation groups, lipid peroxidation in the tumors from irradiated mice increased to 135% and 150%, respectively, four days after irradiation and 33% and 66% in the same groups, respectively, 24 days after irradiation. In general, lipid peroxidation in the rectum did not increase in GT-treated and irradiated mice, although there was a slight increase in Fe-stimulated lipid peroxidation (29%) four days after irradiation. Unexpectedly, the kidneys were as equally sensitized to lipid peroxidation as the tumors. Liver tissue was protected in the short-term from radiation-induced lipid peroxidation. These studies indicate that the radiotherapy efficacy of prostate cancer can be increased with GT and a pro-oxidant if the kidneys can be shielded.
Kumar
K Sree
KS
Radiation Casualty Management Team and Veterinary Sciences Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA. kumar@afrri.usuhs.mil
Raghavan
Mythili
M
Hieber
Kevin
K
Ege
Christine
C
Mog
Steven
S
Parra
Nannette
N
Hildabrand
Annette
A
Singh
Vijay
V
Srinivasan
V
V
Toles
Raymond
R
Karikari
Patience
P
Petrovics
Gyorgy
G
Seed
Thomas
T
Srivastava
Shiv
S
Papas
Andreas
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology*; D007501:Iron / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012007:Rectum / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D000975:Antioxidants; D002839:Chromans; D011838:Radiation-Sensitizing Agents; D014810:Vitamin E; C013649:plastochromanol 8; D007501:Iron