Isoflavones are known to exert anticancer effects. These effects were examined using two isoflavones, biochanin A and daidzein, in a mouse mammary tumor virus (MMTV)-induced spontaneous breast cancer model. Emphasis was placed on isoflavone metabolism by the intestinal microflora and changes in estrogen levels. Germ-free (Gf) mice and their conventionalized (Cv) counterparts were assigned to three diet groups: (1) control diet, (2) biochanin A and (3) daidzein. In all groups, urine was collected from virgin female mice to analyze isoflavone metabolism by high performance liquid chromatography. These studies revealed changes of biochanin A into genistein, and of daidzein into equol, which were accelerated in the Cv animals. However, the Gf mice could not transform biochanin A into genistein, or daidzein into equol. Estrogen levels in the control and daidzein diet groups were lower in the Gf mice than in the Cv mice. The biochanin A group showed no differences in estrogen levels between the Cv and Gf animals. Four-week-old male and female animals were paired in the Gf and Cv groups. The female animals delivered and lactated repeatedly and were observed for the development of mammary cancer by palpation, twice weekly, until 15 months of age. The Cv mice showed a significantly lower incidence of breast cancer in the biochanin A diet group than in the control or daidzein groups (p < 0.05). These results suggest that the anticarcinogenic effects in this system might be produced not by daidzein or equol, but by biochanin A and/or genistein. In the Gf animals, the incidence of breast cancer was significantly higher in the biochanin A group than in the control group (p < 0.05), probably due to the increased level of estradiol in the former group. The biochanin A group tended to have a higher incidence of breast cancer than the daidzein group in the Gf group, although no significant differences were noted. Thus, no anticarcinogenic effect was produced by biochanin A alone in the Gf mice. In view of the results presented, genistein derived from biochanin A following metabolic processes in the intestinal microflora most likely acts as an inhibitor in breast carcinogenesis; biochanin A is most likely a precursor of genistein.

Wu AA, Zieglar RG, Horn-Ross PL, Nomura AMY, West DW, Kolonel LN, Rosenthal JF, Hoover RN, Pike MC: Tofu and risk of breast cancer in Asian-Americans. Cancer Epidemiol Biomarkers Prev 1996;5:901–906.
Tamaya T: Effects of estrogens (in Japanese). Sanfujinka chiryo 1997;74:85–92.
Yoshikawa T: Flavonoid no igaku (in Japanese). Tokyo, Koudansha Scientific, 1998.
Setchell KDR, Addlercreutz H: Mammalian ligands and phyto-oestrogens: Recent studies on their formation, metabolism and biological role in health and disease; in Rowland IR (ed): Role of the Gut Flora in Toxicity and Cancer. New York, Academic Press, 1988, pp 315–345.
Braden AWH, Hart NK, Lamberton JA: The oestrogenic activity and metabolism of certain isoflavones in sheep. Austr J Agric Res 1967;18:335–348.
Shutt DA, Braden AWH: The significance of Equol in relation to the oestrogenic responses in sheep ingesting clover with a high formononetin content. Aust J Agric Res 1968;19:545–553.
Batterham TJ, Shutt DA, Hart NK, Braden AWH, Tweeddale HJ: Metabolism of intraluminally administered [4-14C] formononetin and [4-14C] biochanin A in sheep. Aust J Agric Res 1971;22:131–138.
Barnes S: Effect of genistein on in vitro and in vivo models of cancer. J Nutr 1995;125(3 suppl):777S–783S.
Barnes S, Grubbs C, Kenneth DR, Setchell KDR, Carlson J: Soybeans inhibit mammary tumors in models of breast cancer. Prog Clin Biol 1990;347:239–253.
Lamartiniere CA, Moore JB, Brown NM, Thompson R, Hardin MJ, Barnes S: Genistein suppresses mammary cancer in rats. Carcinogenesis 1995;16:2833–2840.
Lamartiniere CA, Moore J, Holland M, Barnes S: Neonatal genistein chemoprevents mammary cancer. Proc Soc Exp Biol Med 1995;208:120–123.
Lamartiniere CA, Murrill WB, Manzolillo PA, Zhang JX, Barnes S, Zhang X, Wei H, Brown NM: Genistein alters the ontogeny of mammary gland development and protects against chemically-induced mammary cancer in rats. Proc Soc Exp Biol Med 1998;217:358–364.
Murrill WB, Brown NM, Zhang JX, Manzolillo PA, Barnes S, Lamartiniere CA: Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats. Carcinogenesis 1996;17:1451–1457.
Gotoh T, Yamada K, Yin H, Ito A, Kataoka T, Dohi K: Chemoprevention of N-nitroso-N-methylurea-induced rat mammary carcinogenesis by soy foods or biochanin A. Jpn J Cancer Res 1998;89:137–142.
Van Nie R: Mammary tumorigenesis in the GR mouse strain; in Hilgers J, Sluyser M (eds): Mammary Tumors in the Mouse. North-Holland Biomedical Press, Amsterdam, 1981, pp 201–266.
Okada M: The influence of intestinal flora on wound healing in mice. Surg Today 1994;24:347–355.
Franke AA, Custr LJ: High-performance liquid chromatographic analysis of isoflavonoids and coumestrol from human urine. J Chromatogr 1994;662:47–60.
Knight DC, Eden JA: A review of the clinical effects of phytoestrogen. Obstet Gynecol 1996;87:897–904.
Mikssicek RJ: Interaction of naturally occurring nonsteroidal estrogens with expressed recombinant human estrogen receptor. J Steroid Biochem Molec Biol 1994;49:153–160.
Scholar EM, Toews ML: Inhibition of invasion of murine mammary carcinoma cells by the tyrosine kinase inhibitor genistein. Cancer Lett 1994;87:159–162.
Wang C, Kurzer MS: Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells. Nutr Cancer 1997;28:236–247.
Katdare M, Osborne MP, Telang NT: Inhibition of aberrant proliferation and induction of apoptosis in pre-neoplastic human mammary epithelial cells by natural phytochemicals. Oncol Rep 1998;5:311–315.
Matukawa Y, Marui N, Sakai T, Satomi Y, Yoshida M, Matumoto K, Nishino H, Aoike A: Genistein arrests cell cycle progression at G2–M. Cancer Res 1993;53:1328–1331.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.