Anti-tumor-promotion by principles obtained from Angelica keiskei

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.