| Co-Investigator(Kenkyū-buntansha) |
TANIGUCHI Shoko Okayama University. Fac.Pharm.Sci., Res.Assoc., 薬学部, 助手 (20243488)
ITO Hideyuki Okayama University, Fac.Pharm.Sci., Res.Assoc., 薬学部, 助手 (70253002)
HATANO Tsutomu Okayama University, Fac.Pharm.Sci., Assoc.Prof., 薬学部, 助教授 (50127578)
TOKUDA Harukumi Kyoto Pref.Med.University, Res.Assoc., 医学部, 助手 (60111960)
|
|---|
| Research Abstract |
In a search of possible antitumor agents from natural sources, 48 new constituents were obtained from plant species of families Aspidiaceae, Rosaceae, Lythraceae, Melastomataceae, Myrtaceae, and Pinaceae, and their structures were determined based on spectral analyses and chemical method. They included various types of compounds, phloroglucinol derivatives, flavonoids, triterpenoids, sesquiterpene glycosides and hydrolyzable tannins. The compounds of each type were subjected to in vitro primary screening of possible antitumor promoting agent using Raji cells carrying Epstein-Barr virus (EBV) genome. Twenty-four compounds among them showed significant inhibitory effect on activation of EBV early antigen induced by TPA at the concentration of 500 mol ratio/TPA.Their potency was equivalent or stronger than tota of EGCG, a well known anti-tumor promoting agent.
Several compounds which showed in vitro assay were then assessed for two-stage mouse skin carcinogenesis, revealing that the compounds obtained from Eriobotrya japonica, cowania mexicana, Coleogyne ramosissima, Dryopteris fragarans et.exhibited a significant delay of carcinogenesis.
Upon evaluation of cytotoxic activity against human oral tumor cell lines, procyanidin oligomer of E.japonica and Pinus prviflora showed potent cytotoxicity to tumor cells, while they were less toxic to normal cells. This cytotoxic activity was indicated to be attributable to apoptosis-induction by these compounds based on DNA fragmentation on agarlose gel electrophoresis and detection of degradation products of cytokeratin 18 by caspase activation.
Consequently the present study revealed that several plants studied in this project, which contain potent antitumorgenic constituents, would be beneficial to cancer prevention.
|
