Molecular and Cellular Biochemistry

, Volume 421, Issue 1–2, pp 89–101 | Cite as

Beet root juice protects against doxorubicin toxicity in cardiomyocytes while enhancing apoptosis in breast cancer cells

  • Sayantanee Das
  • Scott M. Filippone
  • Denise S. Williams
  • Anindita Das
  • Rakesh C. Kukreja
Article

Abstract

Doxorubicin (DOX, Adriamycin) is a broad-spectrum chemotherapeutic drug used to treat a variety of cancers, although its clinical use is restricted by irreversible cardiotoxicity. Earlier studies show that beet root juice (BRJ), a natural and safe herbal product with high levels of nitrate and antioxidants, is a potent chemopreventive agent; however, its cardioprotective function is yet to be established. The goal of this study was to determine the protective effect of BRJ against DOX-induced cardiotoxicity, and its effect on DOX-induced cytotoxicity in MDA-MB-231 breast cancer cells. Adult rat cardiomyocytes and MDA-MB-231 cells were exposed to different concentrations of BRJ (0.5, 5, 50, 250, and 500 µg/ml) with or without DOX. Cell death, measured by trypan blue staining, was significantly reduced in cardiomyocytes but increased in MDA-MB-231 following 24 h of co-treatment with BRJ and DOX. Cell viability was also significantly reduced after BRJ and DOX co-treatment in MDA-MB-231 cells. Similarly, DOX-induced apoptosis, as determined by TUNEL assay, was significantly reduced following treatment with BRJ for 48 h in cardiomyocytes. In contrast, BRJ significantly increased DOX-mediated apoptosis in cancer cells with activation of poly(ADP-ribose) polymerase (PARP) and increased the Bax:Bcl-2 ratio. DOX-induced generation of reactive oxygen species (ROS) was reduced following co-treatment with BRJ in cardiomyocytes but increased dose-dependently with BRJ in MDA-MB-231 cells. In conclusion, lower concentrations of BRJ with DOX represented the most effective combination of cardioprotection and chemoprevention. These findings provide insight into the possible cardioprotective ability of BRJ in cancer patients treated with anthracycline chemotherapeutic drugs.

Keywords

Apoptosis Beet root juice Breast cancer cells Cardiomyocytes Doxorubicin Reactive oxygen species 

Notes

Acknowledgments

This work was supported by grants from the National Institutes of Health R37HL51045 and RO1 HL118808 to Dr. Rakesh C Kukreja.

Compliance with ethical standards

Conflict of interest

The authors state no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Sayantanee Das
    • 1
    • 4
  • Scott M. Filippone
    • 1
  • Denise S. Williams
    • 2
  • Anindita Das
    • 1
  • Rakesh C. Kukreja
    • 1
    • 3
  1. 1.Division of Cardiology, Department of Internal Medicine, VCU Pauley Heart CenterVirginia Commonwealth UniversityRichmondUSA
  2. 2.Center for Science, Mathematics and TechnologyMills Edwin Godwin High SchoolRichmondUSA
  3. 3.Division of Cardiology, Pauley Heart CenterVirginia Commonwealth UniversityRichmondUSA
  4. 4.Duke UniversityDurhamUSA

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