Normal taste acuity and preference in female adolescents with impaired 6-n-propylthiouracil sensitivity.

This study was conducted to determine the relationship between 6-n-propylthiouracil sensitivity and taste characteristics in female students at Nara Women's University. Participants (n=135) were screened for 6-npropylthiouracil sensitivity using a taste test with 0.56 mM 6-n-propylthiouracil solution, and the sensitivity was confirmed by an assay for the bitter-taste receptor gene, TAS2R38. Based on the screening results, 33 6-npropylthiouracil tasters and 21 non-tasters were enrolled. The basic characteristics that are thought to influence taste acuity, including body mass index, saliva volume and serum micronutrient concentrations (iron, zinc and copper), were similar between the two groups. In an analysis using a filter-paper disc method, there were no differences in the acuity for four basic tastes (sweet, salty, sour and bitter) between 6-n-propylthiouracil tasters and non-tasters. In addition, the taste preference for the four basic tastes as measured by a visual analogue scale was also comparable between the two groups. This is the first study to demonstrate that 6-n-propylthiouracil nontasters have taste sensitivity for the four basic tastes similar to that in 6-n-propylthiouracil tasters, at least in female adolescents, as measured by the gustatory test using a filter-paper disc method.

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.

Apoptosis induction by gamma-tocotrienol in human hepatoma Hep3B cells.

We evaluated the antitumor activity of tocotrienol (T3) on human hepatoma Hep3B cells. At first, we examined the effect of T3 on the proliferation of human hepatoma Hep3B cells and found that gamma-T3 inhibited cell proliferation at lower concentrations and shorter treatment times than alpha-T3. Then, we examined the effect of gamma-T3 apoptosis induction and found that gamma-T3 induced poly (ADP-ribose) polymerase (PARP) cleavage and stimulated a rise in caspase-3 activity. In addition, gamma-T3 stimulated a rise in caspase-8 and caspase-9 activities. We also found that gamma-T3-induced apoptotic cell death was accompanied by up-regulation of Bax and a rise in the fragments of Bid and caspase-8. These data indicate that gamma-T3 induced apoptosis in Hep3B cells and that caspase-8 and caspase-9 were involved in apoptosis induction. Moreover, these results suggest that Bax and Bid regulated apoptosis induction by gamma-T3.

Induction of apoptosis by tocotrienol in rat hepatoma dRLh-84 cells.

Our aim was to evaluate the antitumor activities of tocopherol (Toc) and tocotrienol (T3) derivatives. At first, we examined the effect of these vitamin E homologues on the proliferation of rat normal hepatocyte RLN-10 and hepatoma dRLh-84 cells and found that especially T3 inhibited cell proliferation in dRLh-84 cells. Then, we examined the effect of vitamin E homologues on apoptosis induction and found that T3 induced DNA fragmentation and stimulated a rise of caspase-3 activity. In addition, T3 stimulated a rise in caspase-8 activity, while a caspase-8 inhibitor suppressed apoptosis induction by T3. We also examined the incorporation of vitamin E homologues into dRLh-84 cells. T3 was incorporated more quickly compared to Toc. These results indicated that T3 induces apoptosis in dRLh-84 cells and that caspase-8 is involved in this apoptosis induction. The difference in terms of apoptosis induction by vitamin E homologues seems to be related to their different rates of cellular incorporation.