Resveratrol, a phytoalexin found in grapes and other food products, was purified and shown to have cancer chemopreventive activity in assays representing three major stages of carcinogenesis. Resveratrol was found to act as an antioxidant and antimutagen and to induce phase II drug-metabolizing enzymes (anti-initiation activity); it mediated anti-inflammatory effects and inhibited cyclooxygenase and hydroperoxidase functions (antipromotion activity); and it induced human promyelocytic leukemia cell differentiation (antiprogression activity). In addition, it inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. These data suggest that resveratrol, a common constituent of the human diet, merits investigation as a potential cancer chemopreventive agent in humans.

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As a result of bioassay-guided fractionation, betulinic acid, a pentacyclic triterpene, was identified as a melanoma-specific cytotoxic agent. In follow-up studies conducted with athymic mice carrying human melanomas, tumour growth was completely inhibited without toxicity. As judged by a variety of cellular responses, antitumour activity was mediated by the induction of apoptosis. Betulinic acid is inexpensive and available in abundant supply from common natural sources, notably the bark of white birch trees. The compound is currently undergoing preclinical development for the treatment or prevention of malignant melanoma.

As part of ongoing research on cancer chemopreventive agents from botanical dietary supplements, Garcinia mangostana L. (commonly known as mangosteen) was selected for detailed study. Repeated chromatography of a CH2Cl2-soluble extract of the pericarp led to the isolation of two new highly oxygenated prenylated xanthones, 8-hydroxycudraxanthone G (1) and mangostingone [7-methoxy-2-(3-methyl-2-butenyl)-8-(3-methyl-2-oxo-3-butenyl)-1,3,6-trihydroxyxanthone, 2], together with 12 known xanthones, cudraxanthone G (3), 8-deoxygartanin (4), garcimangosone B (5), garcinone D (6), garcinone E (7), gartanin (8), 1-isomangostin (9), alpha-mangostin (10), gamma-mangostin (11), mangostinone (12), smeathxanthone A (13), and tovophyllin A (14). The structures of compounds 1 and 2 were elucidated by spectroscopic data analysis. Except for compound 2, which was isolated as a minor component, the antioxidant activities of all isolates were determined using authentic and morpholinosydnonimine-derived peroxynitrite methods, and compounds 1, 8, 10, 11, and 13 were the most active. Alpha-mangostin (10) inhibited 7,12-dimethylbenz[alpha]anthracene-induced preneoplastic lesions in a mouse mammary organ culture assay with an IC50 of 1.0 microg/mL (2.44 microM).

Two new compounds, an ent-isopimarane-type diterpene, 3alpha,12alpha-dihydroxy-ent-8(14),15-isopimaradien-18-al (1), and a dihydrobenzo[b]furan neolignan, (-)-trans-9-acetyl-4,9'-di-O-methyl-3'-de-O-methyldehydrodiconiferyl alcohol (2), along with five known compounds, 7,7'-dihydroxy-6,8'-bicoumarin (bicoumol) (3), 3,4-dimethoxycinnamaldehyde (4), 6-hydroxy-7-methoxycoumarin (isoscopoletin), N-butylaniline, and vanillin, have been isolated from an ethyl acetate-soluble extract of the stem wood of Euphorbiaquinquecostata. The structures of compounds 1 and 2 were elucidated on the basis of spectroscopic data interpretation, and single-crystal X-ray diffraction analysis was used to confirm the structure and relative stereochemistry of 1. The absolute configuration of 1 was established by a convenient Mosher ester procedure in which the sample was treated with MTPA chlorides in deuterated pyridine directly in NMR tubes. All isolates were evaluated for the induction of quinone reductase in Hepa1c1c7 hepatoma cells and for the inhibition of the transformation of murine epidermal JB6 cells.