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Effect of isoflavones on breast cancer cell development and their impact on breast cancer treatments

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Abstract

Purpose

Epidemiological studies have suggested that intake of soy isoflavones is associated with a reduced risk of development of breast cancer and an improved prognosis in patients with breast cancer. In addition, basic research has demonstrated the antitumor effects of these compounds on breast cancer cell lines. However, the detailed effects of the intake of equol, which is one of the metabolites of the soy isoflavones, are yet to be clarified on the risk of development and recurrence of breast cancer and its interactions with drugs used for treating breast cancer. This study aimed to determine the antitumor effects of equol and investigate the impact of adding equol to therapeutic agents for breast cancer using breast cancer cell lines.

Methods

We examined the antitumor effect of equol on breast cancer cell lines using MTS assay. We also studied the combined effect of equol and the existing hormonal or chemotherapeutic agents using combination index. We evaluated the expressions of the related proteins by Western blot analysis and correlated the findings with the antitumor effect.

Results

Equol showed bi-phasic protumor and antitumor effects; at a low concentration, it promoted the tumor growth in hormone receptor-positive cell lines, whereas antitumor effects were generally observed when an excessive amount of dose unexpected in the blood and the tissue was administered. When used with tamoxifen, equol might have some antagonistic effect, although it depends on equol concentration and the type of cancer cells.

Conclusions

We confirmed that equol has dual action, specifically a tumor growth-promoting effect and an antitumor effect. Although the results suggested that equol might exert an antagonistic effect against tamoxifen depending on the concentration, equol did not exert an antagonistic effect on other therapeutic agents.

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Acknowledgements

This work was supported by a Management Expenses Grants for National University Corporations in Japan. We thank Dr. Koki Tsuboi and Dr. Shin-ichi Hayashi (Department of Molecular and Functional Dynamics, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan) for providing us with the aromatase-overexpressing MCF-7 cell line (E10arom) for this study.

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Authors and Affiliations

  1. Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Minami Hatono, Hirokuni Ikeda, Yoko Suzuki, Yukiko Kajiwara, Kengo Kawada, Takahiro Tsukioki, Mariko Kochi, Ken Suzawa, Takayuki Iwamoto, Hiromasa Yamamoto, Tadahiko Shien, Masaomi Yamane, Naruto Taira, Hiroyoshi Doihara & Shinichi Toyooka

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  1. Minami Hatono
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  2. Hirokuni Ikeda
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Correspondence to Hirokuni Ikeda.

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Hatono, M., Ikeda, H., Suzuki, Y. et al. Effect of isoflavones on breast cancer cell development and their impact on breast cancer treatments. Breast Cancer Res Treat 185, 307–316 (2021). https://doi.org/10.1007/s10549-020-05957-z

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  • DOI: https://doi.org/10.1007/s10549-020-05957-z

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