Sulforaphane diminishes the formation of mammary tumors in rats exposed to 17β-estradiol

Dushani L. Palliyaguru, Li Yang, Dionysios V. Chartoumpekis, Stacy G. Wendell, Marco Fazzari, John J. Skoko, Yong Liao, Steffi Oesterreich, George K. Michalopoulos, Thomas W. Kensler

Research output: Contribution to journalArticlepeer-review

Abstract

Elevated levels of estrogen are a risk factor for breast cancer. In addition to inducing DNA damage, estrogens can enhance cell proliferation as well as modulate fatty acid metabolism that collectively contributes to mammary tumorigenesis. Sulforaphane (SFN) is an isothiocyanate derived from broccoli that is currently under evaluation in multiple clinical trials for prevention of several diseases, including cancer. Previous studies showed that SFN suppressed DNA damage and lipogenesis pathways. Therefore, we hypothesized that administering SFN to animals that are co-exposed to 17β-estradiol (E2) would prevent mammary tumor formation. In our study, 4–6 week old female August Copenhagen Irish rats were implanted with slow-release E2 pellets (3 mg × 3 times) and gavaged 3x/week with either vehicle or 100 µmol/kg SFN for 56 weeks. SFN-treated rats were protected significantly against mammary tumor formation compared to vehicle controls. Mammary glands of SFN-treated rats showed decreased DNA damage while serum free fatty acids and triglyceride species were 1.5 to 2-fold lower in SFN-treated rats. Further characterization also showed that SFN diminished expression of enzymes involved in mammary gland lipogenesis. This study indicated that SFN protects against breast cancer development through multiple potential mechanisms in a clinically relevant hormonal carcinogenesis model.

Original languageEnglish (US)
Article number2282
Pages (from-to)1-15
Number of pages15
JournalNutrients
Volume12
Issue number8
DOIs
StatePublished - Aug 2020
Externally publishedYes

Keywords

  • Breast cancer
  • Estrogen
  • Lipid metabolism
  • Prevention
  • Sulforaphane

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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