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PLoS One. 2018 Mar 8;13(3):e0193918. doi: 10.1371/journal.pone.0193918. eCollection 2018.

Sulforaphane potentiates anticancer effects of doxorubicin and attenuates its cardiotoxicity in a breast cancer model.

Author information

1
University of Arkansas for Medical Sciences, Department of Geriatrics, Little Rock, Arkansas, United States of America.
2
Texas Tech Health Sciences Center, Division of Hematology & Oncology, Department of Internal Medicine, Lubbock, Texas, United States of America.
3
University of Arkansas for Medical Sciences, Department of Pharmacology and Toxicology, Little Rock, Arkansas, United States of America.
4
University of Arkansas for Medical Sciences, Department of Neurobiology and Developmental Sciences, Little Rock, Arkansas, United States of America.
5
University of Arkansas for Medical Sciences, Division of Radiation Health, Little Rock, Arkansas, United States of America.
6
Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.

Abstract

Breast cancer is the most common malignancy in women of the Western world. Doxorubicin (DOX) continues to be used extensively to treat early-stage or node-positive breast cancer, human epidermal growth factor receptor-2 (HER2)-positive breast cancer, and metastatic disease. We have previously demonstrated in a mouse model that sulforaphane (SFN), an isothiocyanate isolated from cruciferous vegetables, protects the heart from DOX-induced toxicity and damage. However, the effects of SFN on the chemotherapeutic efficacy of DOX in breast cancer are not known. Present studies were designed to investigate whether SFN alters the effects of DOX on breast cancer regression while also acting as a cardioprotective agent. Studies on rat neonatal cardiomyocytes and multiple rat and human breast cancer cell lines revealed that SFN protects cardiac cells but not cancer cells from DOX toxicity. Results of studies in a rat orthotopic breast cancer model indicated that SFN enhanced the efficacy of DOX in regression of tumor growth, and that the DOX dosage required to treat the tumor could be reduced when SFN was administered concomitantly. Additionally, SFN enhanced mitochondrial respiration in the hearts of DOX-treated rats and reduced cardiac oxidative stress caused by DOX, as evidenced by the inhibition of lipid peroxidation, the activation of NF-E2-related factor 2 (Nrf2) and associated antioxidant enzymes. These studies indicate that SFN not only acts synergistically with DOX in cancer regression, but also protects the heart from DOX toxicity through Nrf2 activation and protection of mitochondrial integrity and functions.

PMID:
29518137
PMCID:
PMC5843244
DOI:
10.1371/journal.pone.0193918
[Indexed for MEDLINE]
Free PMC Article

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