Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells

Chuanfeng Wang, Mindy S. Kurzer

Research output: Contribution to journalArticlepeer-review

232 Scopus citations

Abstract

Thirteen isoflavonoid, flavonoids, and lignans, including some known phytoestrogens, were evaluated for their effects on DNA synthesis in estrogen-dependent (MCF7) and -independent (MDA-MB-231) human breast cancer cells. Treatment for 24 hours with most of the compounds at 20-80 μM sharply inhibited DNA synthesis in MDA-MB-231 cells. In MCF-7 cells, on the other hand, biphasic effects were seen. At 0.1-10 μM, coumestrol, genistein, biochanin A, apigenin, luteolin, kaempferol, and enterolactone reduced DNA synthesis 150-235% and, at 20-90 μM, inhibited DNA synthesis bY 50%. Treatment of MCF-7 cells for 10 days with genistein or coumestrol showed continuous stimulation of DNA synthesis at low concentrations. Time-course experiments with genistein in MCF-7 cells showed effects to be reversed by 48-hour withdrawal of genistein at most concentrations. Induction of DNA synthesis in MCF-7 cells, but not in MDA-MB-231 cells, is consistent with an estrogenic effect of these compounds. Inhibition of estrogen-dependent and - independent breast cancer cells at high concentrations suggests additional mechanisms independent of the estrogen receptor. The current focus on the role of phytoestrogens in cancer prevention must take into account the biphasic effects observed in this study, showing inhibition of DNA synthesis at high concentrations but induction at concentrations close to probable levels in humans.

Original languageEnglish (US)
Pages (from-to)236-247
Number of pages12
JournalNutrition and Cancer
Volume28
Issue number3
DOIs
StatePublished - 1997

Bibliographical note

Funding Information:
This work was performed in the Department of Food Science and Nutrition, University of Minnesota. It was supported in part by Minnesota Agricultural Experiment Station Project 18-34. These data were presented in part at the Annual Meeting of the American Association for Cancer Research, Washington, DC, April 1996. Address reprint requests to Dr. Mindy S. Kurzer, Dept. of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55108. Phone: (612) 624-9789. FAX: (612) 625-5272. E-mail: kurze001 @maroon.tc.umn.edu.

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