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Three neolignans, known as magnolol [1], honokiol [2] and the new monoterpenylmagnolol [3], were isolated from the bark of Magnolia officinalis as inhibitors of Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The structure of 3 was determined from 2D nmr spectral data and difference nOe experiments. The MeOH extract of this plant and magnolol exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two stage carcinogenesis test. This investigation indicates that these neolignans and the extract might be valuable antitumor promoters.

Yeast cells take up thiamin from the extracellular environment by an active transport system with a pH optimum of 4.5 and a K m value of 0.18 M, and thiamin in the cells is concentrated ϳ10,000-fold over extracellular levels (1). The thiamin transport system is more specific for the chemical structure of the pyrimidine moiety than the thiazole moiety of thiamin (2). Saccharomyces cerevisiae also secretes a thiamin-repressible acid phosphatase encoded by PHO3 gene (3, 4) in a periplasmic space. Since yeast cells cannot take up thiamin phosphate esters, the PHO3 protein with a high affinity for thiamin phosphate esters appears to hydrolyze them before the uptake (5, 6), and then thiamin is converted to thiamin pyrophosphate (TPP) 1 by thiamin pyrophosphokinase (EC 2.7.6.2) encoded by the THI80 gene (7). TPP is an important cofactor in the energy metabolism (8) and is a negative effector of the regulation mechanism of thiamin metabolism in yeast cells (9).We report here the isolation and characterization of S. cerevisiae THI10 gene and provide evidence that the THI10 gene encodes for a thiamin transport carrier protein. The predicted THI10 protein is highly hydrophobic and shows significant sequence similarities to yeast uracil and allantoin transport proteins. The thiamin transport activity and the thiamin binding activity in the yeast plasma membrane fraction in thi10 null strain cells were restored when the THI10 open reading frame (ORF) was expressed by yeast GAL1 promoter. The regulation of the THI10 gene expression was also investigated.

Potent anti-tumor promoter activity has been found in the nonpolar extracts of the root of "Ashita-Ba", Angelica keiskei Koidz. (Umbelliferae), which is eaten as a vegetable in Japan. From this active fraction, two angular furanocoumarins, archangelicin (1) and 8(S),9(R)-9-angeloyloxy-8,9-dihydrooroselol (2), three linear furanocoumarins, psoralen (3), bergapten (4) and xanthotoxin (5), and three chalcones, 4-hydroxyderricin (6), xanthoangelol (7) and a novel chalcone named ashitaba-chalcone (8), were isolated. Among these compounds, two angular type furanocoumarins, 1 and 2, and three chalcones, 6-8, suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated 32Pi-incorporation into phospholipids of cultured cells, whereas coumarins 3-5 were less effective. In addition, chalcones 6 and 7 were proved to have anti-tumor-promoting activity in mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) plus TPA. Since chalcones 6 and 7 showed calmodulin-interacting property, both chalcones may reveal anti-tumor-promoting activity via the modulation of calmodulin involved systems. These chalcones may be useful to develop the effective method for cancer prevention.

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