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Volume 22
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10.3390/ijms22147439
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Article

Cytoprotective Effect of Vitamin D on Doxorubicin-Induced Cardiac Toxicity in Triple Negative Breast Cancer

by
Kevin J Lee
1,*,
Griffin Wright
1,
Hannah Bryant
2,
Leigh Ann Wiggins
2,
Valeria L. Dal Zotto
3,
Michele Schuler
2,4,
Christopher Malozzi
5,
Michael V Cohen
1,5 and
Natalie R Gassman
1,*
1
Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile, AL 36688, USA
2
Department of Comparative Medicine, University of South Alabama College of Medicine, Mobile, AL 36688, USA
3
Department of Pathology and Laboratory Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
4
Department of Microbiology and Immunology, University of South Alabama College of Medicine, Mobile, AL 36688, USA
5
Department of Medicine, University of South Alabama College of Medicine, Mobile, AL 36688, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(14), 7439; https://doi.org/10.3390/ijms22147439
Submission received: 14 June 2021 / Revised: 6 July 2021 / Accepted: 7 July 2021 / Published: 12 July 2021
(This article belongs to the Special Issue Molecular Target and Action Mechanism of Anti-Cancer Agents)
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Abstract

Background: Doxorubicin (Dox) is a first-line treatment for triple negative breast cancer (TNBC), but its use may be limited by its cardiotoxicity mediated by the production of reactive oxygen species. We evaluated whether vitamin D may prevent Dox-induced cardiotoxicity in a mouse TNBC model. Methods: Female Balb/c mice received rodent chow with vitamin D3 (1500 IU/kg; vehicle) or chow supplemented with additional vitamin D3 (total, 11,500 IU/kg). the mice were inoculated with TNBC tumors and treated with intraperitoneal Dox (6 or 10 mg/kg). Cardiac function was evaluated with transthoracic echocardiography. The cardiac tissue was evaluated with immunohistochemistry and immunoblot for levels of 4-hydroxynonenal, NAD(P)H quinone oxidoreductase (NQO1), C-MYC, and dynamin-related protein 1 (DRP1) phosphorylation. Results: At 15 to 18 days, the mean ejection fraction, stroke volume, and fractional shortening were similar between the mice treated with vitamin D + Dox (10 mg/kg) vs. vehicle but significantly greater in mice treated with vitamin D + Dox (10 mg/kg) vs. Dox (10 mg/kg). Dox (10 mg/kg) increased the cardiac tissue levels of 4-hydroxynonenal, NQO1, C-MYC, and DRP1 phosphorylation at serine 616, but these increases were not observed with vitamin D + Dox (10 mg/kg). A decreased tumor volume was observed with Dox (10 mg/kg) and vitamin D + Dox (10 mg/kg). Conclusions: Vitamin D supplementation decreased Dox-induced cardiotoxicity by decreasing the reactive oxygen species and mitochondrial damage, and did not decrease the anticancer efficacy of Dox against TNBC.
Keywords: antioxidant; oncology; cardiology; reactive oxygen species; chemotherapy antioxidant; oncology; cardiology; reactive oxygen species; chemotherapy
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MDPI and ACS Style

Lee, K.J.; Wright, G.; Bryant, H.; Wiggins, L.A.; Dal Zotto, V.L.; Schuler, M.; Malozzi, C.; Cohen, M.V.; Gassman, N.R. Cytoprotective Effect of Vitamin D on Doxorubicin-Induced Cardiac Toxicity in Triple Negative Breast Cancer. Int. J. Mol. Sci. 2021, 22, 7439. https://doi.org/10.3390/ijms22147439

AMA Style

Lee KJ, Wright G, Bryant H, Wiggins LA, Dal Zotto VL, Schuler M, Malozzi C, Cohen MV, Gassman NR. Cytoprotective Effect of Vitamin D on Doxorubicin-Induced Cardiac Toxicity in Triple Negative Breast Cancer. International Journal of Molecular Sciences. 2021; 22(14):7439. https://doi.org/10.3390/ijms22147439

Chicago/Turabian Style

Lee, Kevin J, Griffin Wright, Hannah Bryant, Leigh Ann Wiggins, Valeria L. Dal Zotto, Michele Schuler, Christopher Malozzi, Michael V Cohen, and Natalie R Gassman. 2021. "Cytoprotective Effect of Vitamin D on Doxorubicin-Induced Cardiac Toxicity in Triple Negative Breast Cancer" International Journal of Molecular Sciences 22, no. 14: 7439. https://doi.org/10.3390/ijms22147439

APA Style

Lee, K. J., Wright, G., Bryant, H., Wiggins, L. A., Dal Zotto, V. L., Schuler, M., Malozzi, C., Cohen, M. V., & Gassman, N. R. (2021). Cytoprotective Effect of Vitamin D on Doxorubicin-Induced Cardiac Toxicity in Triple Negative Breast Cancer. International Journal of Molecular Sciences, 22(14), 7439. https://doi.org/10.3390/ijms22147439

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