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

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 demons...

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Bibliographic Details
Published in:PloS one 2018-03, Vol.13 (3), p.e0193918
Main Authors: Bose, Chhanda, Awasthi, Sanjay, Sharma, Rajendra, Beneš, Helen, Hauer-Jensen, Martin, Boerma, Marjan, Singh, Sharda P
Format: Article
Language:English
Subjects:
Activation
Animals
Anticancer properties
Anticarcinogenic Agents - administration & dosage
Anticarcinogenic Agents - pharmacology
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - toxicity
Antioxidants
Biology and Life Sciences
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Cancer
Cancer therapies
Cardiomyocytes
Cardiotoxicity
Cardiotoxicity - prevention & control
Care and treatment
Cell cycle
Cell Line, Tumor
Chemotherapy
Complications and side effects
Cytokines - blood
Dosage and administration
Doxorubicin
Doxorubicin - administration & dosage
Doxorubicin - toxicity
Drug Synergism
Electron transport
Epidermal growth factor
ErbB-2 protein
Female
Health sciences
Heart
Heart diseases
Hematology
Humans
Internal medicine
Isothiocyanate
Isothiocyanates - administration & dosage
Isothiocyanates - pharmacology
Lipid peroxidation
Lipid Peroxidation - drug effects
Malignancy
Mammary Neoplasms, Experimental - drug therapy
Medical research
Medicine and Health Sciences
Metastases
Mitochondria
Mitochondria, Heart - drug effects
Myocytes, Cardiac - drug effects
Neonates
Neurosciences
NF-E2-Related Factor 2 - metabolism
Oxidation-Reduction
Oxidative Phosphorylation - drug effects
Oxidative stress
Oxidative Stress - drug effects
Peroxidation
Rats
Rats, Sprague-Dawley
Regression
Rodents
Sulforaphane
Toxicity
Toxicology
Transcription factors
Trends
Tumor cell lines
Tumorigenesis
Vegetables
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0193918