Cancer Chemopreventive Activity of Rotenoids from Derris trifoliata

Abstract

A study of the chemical constituents of the stems of Derris trifoliata Lour. (Leguminosae) led to the isolation and identification of one new rotenoid, 6aα,12aα-12a-hydroxyelliptone (3), together with five other known rotenoids. In a search for novel cancer chemopreventive agents (anti-tumor promoters), we carried out a primary screening of five of the rotenoids isolated from the plant for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells. The inhibitory activity of 3 was found to be equivalent to that of β-carotene without any cytotoxicity. Deguelin (4) and α-toxicarol (5) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. This investigation indicated that rotenoids might be valuable anti-tumor promoters.

Key words

Derris trifoliata - Leguminosae - rotenoid - cancer chemopreventive agents - anti-tumor promoters

References

• 1 Kan W S. Manual of Medicinal Plants in Taiwan. Vol. 2 National Research Institute of Chinese Medicine Taiwan; 1972: pp 276-80
• 2 Li L, Wang H K, Chang J J, McPhail A T, McPhail D R, Terada H. et al . Antitumor agents, 138. Rotenoids and isoflavones as cytotoxic constituents from Amorpha fruticosa .  Journal of Natural Products. 1993;  56 690-8
• 3 Udeani G O, Zhao G M, Shin Y G, Kosmeder JW 2 nd, Beecher C WW, Kinghorn A D. et al . Pharmacokinetics of deguelin, a cancer chemopreventive agent in rats.  Cancer Chemotherapy and Pharmacology. 2001;  47 263-8
• 4 Udeani G O, Gerhäuser C, Thomas C F, Moon R C, Kosmeder J W, Kinghorn A D. et al . Cancer chemopreventive activity mediated by deguelin, a naturally occurring rotenoid.  Cancer Research. 1997;  57 3424-8
• 5 Gerhäuser C, Lee S K, Kosmeder J W, Moriarty R M, Hamel E, Mehta R G. et al . Regulation of ornithine decarboxylase induction by deguelin, a natural product cancer chemopreventive agent.  Cancer Research. 1997;  57 3429-35
• 6 Gerhäuser C, Mar W, Lee S K, Suh N, Luo Y, Kosmeder J. et al . Rotenoids mediate potent cancer chemopreventive activity through transcriptional regulation of ornithine decarboxylase.  Nature Medicine. 1995;  1 260-6
• 7 Konoshima T, Terada H, Kokumai M, Kozuka M, Tokuda H, Estes J R. et al . Studies on inhibitors of skin tumor promotion, XII. Rotenoids from Amorpha fruticosa .  Journal of Natural Products. 1993;  56 843-8
• 8 Lin L -J, Ruangrungsi N, Cordell G A, Shieh H- L, You M, Pezzuto J M. 6-Deoxyclitoriacetal from Clitoria macrophylla .  Phytochemistry. 1992;  31 4329-31
• 9 Tahara S, Narita E, Ingham J L, Mizutani J. New rotenoids from the root bark of Jamaican dogwood (Piscidia erythrina L.)  Zeitschrift fur Naturforschung. 1990;  45c 154-60
• 10 Ollis W D, Rhodes C A, Sutherland I O. The extractives of Millettia dura (Dunn). The constitutions of durlettone, durmillone, milldurone, millettone and millettosin.  Tetrahedron. 1967;  23 4741-60
• 11 Thasana N, Chuankamnerdkarn M, Ruchirawat S. A new 12a-hydroxyelliptone from the stems of Derris malaccensis .  Heterocycles. 2001;  55 1121-5
• 12 Carlson D G, Weisleder D, Tallent W H. NMR investigations of rotenoids.  Tetrahedron. 1973;  29 2731-41
• 13 Murakami A, Ohigashi H, Koshimizu K. Anti-tumor promotion with food phytochemicals: A strategy for cancer chemoprevention.  Bioscience Biotechnology and Biochemistry. 1996;  60 1-8