Sulforaphane Diminishes the Formation of Mammary Tumors in Rats Exposed to 17β-Estradiol
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA
Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA
Department of Toxic Substances Control, California Environmental Protection Agency, Cypress, CA 90630, USA
Department of Internal Medicine, Division of Endocrinology, University of Patras, 26504 Patras, Greece
Magee Women’s Research Institute, Pittsburgh, PA 15213, USA
UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA
Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, USA
Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2020, 12(8), 2282; https://doi.org/10.3390/nu12082282
Received: 3 July 2020 / Revised: 26 July 2020 / Accepted: 28 July 2020 / Published: 30 July 2020
(This article belongs to the Section Phytochemicals and Human Health)
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 x 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.