title: Beet root juice protects against doxorubicin toxicity in cardiomyocytes while enhancing apoptosis in breast cancer cells.
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.
authors: Division of Cardiology, Department of Internal Medicine, VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, 23298, USA.|Duke University, Durham, NC, 27708, USA.
authors: Sayantanee
authors: S
authors: Das
authors: Division of Cardiology, Department of Internal Medicine, VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, 23298, USA.
authors: Scott M
authors: SM
authors: Filippone
authors: Center for Science, Mathematics and Technology, Mills Edwin Godwin High School, Richmond, VA, 23238, USA.
authors: Denise S
authors: DS
authors: Williams
authors: Division of Cardiology, Department of Internal Medicine, VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, 23298, USA.
authors: Anindita
authors: A
authors: Das
authors: Division of Cardiology, Department of Internal Medicine, VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, 23298, USA. rakesh.kukreja@vcuhealth.org.|Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020D, Richmond, VA, 23298-0204, USA. rakesh.kukreja@vcuhealth.org.
authors: Rakesh C
authors: RC
authors: Kukreja
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D027461:Beta vulgaris; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004317:Doxorubicin / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D000067030:Fruit and Vegetable Juices; D006801:Humans; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018517:Plant Roots; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; D004317:Doxorubicin
keywords: Apoptosis; Beet root juice; Breast cancer cells; Cardiomyocytes; Doxorubicin; Reactive oxygen species