Anti-tumor-promoting activity of lignans from the aerial part of Saussurea medusa

Abstract

In the course of our continuing search for novel cancer chemopreventive agents from natural sources, several kinds of Compositae plants were screened. Consequently, the lignans, arctiin (ARC) and arctigenin (ARC-G), were obtained from the aerial part of Saussurea medusaas active constituents. These compounds exhibited the remarkable anti-tumor-promoting effect on two-stage carcinogenesis test of mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene as an initiator and 12-O-tetradecanoyl phorbol-13-acetate as a promoter by both topical application and oral administration. Furthermore, ARC-G exhibited potent anti-tumor-promoting activity on two-stage carcinogenesis test of mouse pulmonary tumors induced by 4-nitroquinoline-N-oxide as an initiator and glycerol as a promoter.

Introduction

For the chemoprevention of chemical carcinogenesis, the development of anti-tumor-promoters has been regarded as one of the most effective method [1]. To search for possible cancer chemopreventive agents from natural sources, we have carried out the primary in vitro assay indicated by the inhibitory effects on Epstein–Barr virus early antigen (EBV-EA) activation induced by a well-known promoter, 12-O-tetradecanoyl-13-acetate (TPA), and have examined the two-stage carcinogenesis tests of mouse skin using 7,12-dimethylbenz[a]anthracene (DMBA)/TPA [2], [3], [4], [5], [6], [7], [8]. In the course of our continuing study, several lignans, asarinin from Asiasarum heterotropoides and magnolol from Magnolia officinalis, exhibited the significant chemopreventive effects on two-stage carcinogenesis [9], [10]. On the other hand, the aerial part of Saussurea medusa (compositae) has been used for the treatment of many serious diseases, especially treatment of rheumatoid diseases and for enhancing physical strength in the Northwestern part of China as Thibetan and Nepalese traditional and folk medicines. Bioassay-directed fractionation of the foregoing active extract led to the isolation and characterization of two active lignans, arctiin (ARC) and arctigenin (ARC-G) from S. medusa.

In the present study, we report the inhibitory effects of ARC and ARC-G on mouse two-stage skin carcinogenesis model using DMBA as an initiator and TPA as a promoter by topical application and oral administration, and on mouse pulmonary carcinogenesis test using 4-nitroquinoline-N-oxide (4-NQO) as an initiator and glycerol as a promoter [3], [11], [12], [13], [14], [15].