Specific accumulation of gamma- and delta-tocotrienols in tumor and their antitumor effect in vivo.
In contrast to extensive studies on tocopherols, very little is understood about tocotrienols (T3). We evaluated the antitumor activities of gamma-T3 and delta-T3 in murine hepatoma MH134 cells in vitro and in vivo. We found that delta-T3 inhibited the growth of MH134 cells more strongly than gamma-T3 by inducing apoptosis. In C3H/HeN mice implanted with MH134, it was found that gamma-T3 and delta-T3 feeding significantly delayed tumor growth. On the other hand, both T3 had no significant effect on body weight, normal-tissue weight and immunoglobulin levels. Intriguingly, we found that T3 was detected in tumor, but not in normal tissues. These results, to our knowledge, are the first demonstration of specific accumulation of gamma-T3 and delta-T3 in tumors and suggest that T3 accumulation is critical for the antitumor activities of T3.
Hiura
Yuhei
Y
Faculty of Agriculture, Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Kyushu University, Fukuoka 812-8581, Japan.
Tachibana
Hirofumi
H
Arakawa
Ryo
R
Aoyama
Natsuki
N
Okabe
Masaaki
M
Sakai
Midori
M
Yamada
Koji
K
D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D000906:Antibodies / Q000097:blood; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000032:analysis / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002839:Chromans / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry; D008114:Liver Neoplasms, Experimental / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D008168:Lung / Q000737:chemistry; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000166:cytology; D047368:Tumor Burden / Q000187:drug effects; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000032:analysis
D000906:Antibodies; D000970:Antineoplastic Agents; D000975:Antioxidants; D002839:Chromans; D014810:Vitamin E; C082097:tocotrienol, delta; C013649:plastochromanol 8; D024502:alpha-Tocopherol