Studies on the Antitumor-Promoting Activity of Naturally Occurring Substances: II: 1) Inhibition of Tumor-Promoter-Enhanced Phospholipid Metabolism by Umbelliferous Materials

Abstract

Ninety-five extracts prepared from 14 kinds of Umbelliferous materials were studied to determine their effects on tumor-promoter-induced phenomena in vitro. Of the materials, 5 Chinese crude drugs, two Bai-Hua Qian-Hu classified as Q-I and Q-II types, the root of Peucedanum praeruptorum dunn., Zi-Hua Qian-Hu, the root of P. decursivum maxim., Tang-Bai-Zhi, the root of Angelica dahurica benth.et hook. var. pai-chi kimura, hataet yen., Dang-Gui, the root of A. acutiloba kitagawa and 2 Umbelliferous plants, ashita-ba, A. keiskei koidz., and ama-nyuu, A. edulis miyabe, showed potent inhibitory effects on 12-O-tetradecanoylphorbol- 13-acetate (TPA)-stimulated 32Pi incorporation into phospholipids of cultured cells. From the active fraction of the crude drug “Tang-Bai-Zhi,” imperatoin (1), isoimperatoin (2), oxypeucedanin (3), pabulenol (4), neobyakangelicol (5) and byakangelicin (6) were identified as active or inactive principles. Compound 4 had not previously been isolated from Tang-Bai-Zhi, A. dahurica var. pai-chi. We also discuss the structure-activity relationship among the above 6 kinds of linear-type furanocoumarins, together with 3 kinds of antitumor-promoter coumarins having the same skeleton, psoralen (7), bergapten (8) and xanthotoxin (9), obtained from “ashita-ba” (eaten as a vegetable in Japan). Among the compounds in the present experiment, compounds 1 and 2 showed potent inhibitory activity at the concentration of 50 pg/ml and 3—9 were found to have less or no activity. © 1990, The Pharmaceutical Society of Japan. All rights reserved.