ELSEVIER Mutation Research 370 (1996) 127-131 Genetic Toxicology Antimutagenic and anticarcinogenic activity of natural and synthetic curcuminoids Ruby John Anto a, Josely George a, K.V. Dinesh Babu b, K.N. Rajasekharan b, Ramadasan Kuttan ag * a Amala Cancer Research Centre, Amala Nagar, Thrissur 680 553, Kerala, India b Department of Chemistry, University of Kerala, Triuandrum, India Received 24 October 1995; revised 19 March 1996; accepted 28 May 1996 Abstract Five synthetic curcuminoids and three natural curcuminoids were investigated for their antimutagenic and anti-promo- tional activity. The natural curcuminoids, curcumin I (diferuloylmethane), curcumin II (feruloyl-p-hydroxycin- namoylmethane) and curcumin III (his-( p-hydroxycinnamoyl)methane) isolated from Curcuma longa were found to be potent inhibitors of mutagenesis and crotean oil-induced tumour promotion. Curcumin III produced 87.6% inhibition to 2-acetamidofluorene (2-AAF) induced mutagenesis, at a concentration of 100 pg/plate, curcumin II and curcumin I produced 70.5% and 68.3% inhibition at the same concentration. All the synthetic curcuminoids were found to inhibit 2-AAF-induced mutagenicity among which salicyl- and anisylcurcuminoidswere the most active. Curcumin III was the most effective anti-promotor among natural curcuminoids. While 90% of the control animals were having papillomas on the 10th week of tumour initiation, only 10% of the curcumin III-treated animals, 20% of the curcumin II-treated animals, and 40% of the curcumin I-treated animals were having papillomas. Salicylcurcuminoid, which was causing no papillomas by the 10th week, was the most potent anti-carcinogen among the synthetic curcuminoids. Piperonal curcuminoid also exhibited anti-promotional activity. Keywords: Curcuminoid; Anticarcinogenic activity 1. Introduction ears [3]. It has been suggested that the hydroxy Curcumin, identified as the major pigment in turmeric and a known antioxidant [l], has already been tested for its antimutagenic [2] and anticarcino- genie [3,4] activity. Topical application of curcumin inhibited TPA-induced epidermal DNA synthesis tu- mour promotion in mouse skin and oedema of mouse * Corresponding author. groups on the benzene rings, double bonds in the alkene portion of the molecule and/or the central B-diketone moiety could be responsible for the high biological activity of curcumin [5,6]. This sugges- tion, along with the supporting data obtained for the antitumour and antioxidant activity of compounds having curcuminoid structure [6,7], made us conduct further studies on the antimutagenic and antipromo- tional activity of synthetic and natural curcuminoids. 0165-1218/96/$15.00 Copyright 0 1996 Elsevier Science All rights reserved. PII SO165-1218(96)00074-2