coumestrol and Cell-Transformation--Neoplastic

For the simultaneous assessment of in vitro carcinogenicity and mutagenicity of phytoestrogens, the abilities of 5 phytoestrogens, daidzein, genistein, biochanin A, prunetin, and coumestrol, to induce cell transformation and genetic effects were examined using the Syrian hamster embryo (SHE) cell model. Cellular growth was inhibited by all phytoestrogens in a concentration-related manner. The growth inhibitory effect of the compounds was ranked: genistein, prunetin > coumestrol > biochanin A > daidzein, which did not correspond to their apoptosis-inducing abilities. Morphological transformation in SHE cells was elicited by all phytoestrogens, except, prunetin. The transforming activities were ranked as follows: genistein > coumestrol > daidzein > biochanin A. Somatic mutations in SHE cells at the Na(+)/K(+) ATPase and hprt loci were induced only by genistein, coumestrol, or daidzein. Chromosome aberrations were induced by genistein or coumestrol, and aneuploidy in the near diploid range was occurred by genistein or biochanin A. Genistein, biochanin A or daidzein induced DNA adduct formation in SHE cells with the abilities: genistein > biochanin A > daidzein. Prunetin was negative for any of these genetic endpoints. Our results provide evidence that genistein, coumestrol, daidzein and biochanin A induce cell transformation in SHE cells and that the transforming activities of these phytoestrogens correspond to at least 2 of the mutagenic effects by each phytoestrogen, i.e., gene mutations, chromosome aberrations, aneuploidy or DNA adduct formation, suggesting the possible involvement of mutagenicity in the initiation of phytoestrogen-induced carcinogenesis.

Topics: Animals; Anticarcinogenic Agents; Apoptosis; Cell Line; Cell Transformation, Neoplastic; Chromosome Aberrations; Coumestrol; Cricetinae; DNA Adducts; Dose-Response Relationship, Drug; Embryo, Mammalian; Estrogens, Non-Steroidal; Genistein; Isoflavones; Mesocricetus; Metaphase; Models, Chemical; Mutagens; Mutation; Phytoestrogens; Plant Preparations; Time Factors

Prostate cancer is one of the most common male cancers in Western countries, yet the incidence of this fatal disease remains low in Asian populations. Environmental factors such as diet play an important role in hormone-dependent cancer etiology, and a high phytoestrogen intake may be one factor contributing to the low prostate cancer mortality in Eastern populations. In this study, we investigated the effects of the phytoestrogens genistein, daidzein, coumestrol, and equol on cell growth and DNA damage (strand breakage) in two human prostate tumor cell lines: androgen receptor-positive LNCaP and androgen receptor-negative PC-3. Each compound caused growth inhibition at physiologically relevant concentrations (<10 microM). Genistein induced DNA damage in both cell lines at <10 microM. Daidzein inhibited cell growth at 10-100 microM yet had no effect on DNA damage at up to 500 microM. Thus, despite their structural similarities, different phytoestrogens inhibit prostate tumor cell growth by independent mechanisms.

Topics: Antineoplastic Agents, Phytogenic; Cell Division; Cell Transformation, Neoplastic; Chromans; Coumestrol; DNA Damage; Equol; Estrogens, Non-Steroidal; Genistein; Humans; Isoflavones; Male; Phytoestrogens; Plant Preparations; Prostatic Neoplasms; Tumor Cells, Cultured