Email updates

Keep up to date with the latest news and content from BMC Complementary and Alternative Medicine and BioMed Central.

Open Access Research article

Protective effect of guggulsterone against cardiomyocyte injury induced by doxorubicin in vitro

Wen-Ching Wang1, Yih-Huei Uen12, Ming-Long Chang3, Khoot-Peng Cheah3, Joe-Sharg Li3, Wen-Yu Yu3, Kock-Chee Lee3, Cheuk-Sing Choy45 and Chien-Ming Hu35*

Author Affiliations

1 Department of Surgery; Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan

2 Department of Medical Research Chi Mei Medical Center, Tainan, Institute of Biomedical Engineering, Southern Taiwan University, Tainan, Taiwan

3 Emergency Department, Taipei Medical University Hospital, Taipei, Taiwan

4 Taipei Hospital, Department of Health, Taipei, Taiwan

5 Department of Primary Care Medicine, School of Medicine, College of Medicine, Taipei Medical University; Emergency Department, Taipei Medical University Hospital, Wu-Xing Street, Taipei, 110, Taiwan

For all author emails, please log on.

BMC Complementary and Alternative Medicine 2012, 12:138  doi:10.1186/1472-6882-12-138

Published: 27 August 2012

Abstract

Background

Doxorubicin (DOX) is an effective antineoplastic drug; however, clinical use of DOX is limited by its dose-dependent cardiotoxicity. It is well known that reactive oxygen species (ROS) play a vital role in the pathological process of DOX-induced cardiotoxicity. For this study, we evaluated the protective effects of guggulsterone (GS), a steroid obtained from myrrh, to determine its preliminary mechanisms in defending against DOX-induced cytotoxicity in H9C2 cells.

Methods

In this study, we used a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release measurements, and Hoechst 33258 staining to evaluate the protective effect of GS against DOX-induced cytotoxicity in H9C2 cells. In addition, we observed the immunofluorescence of intracellular ROS and measured lipid peroxidation, caspase-3 activity, and apoptosis-related proteins by using Western blotting.

Results

The MTT assay and LDH release showed that treatment using GS (1–30 μM) did not cause cytotoxicity. Furthermore, GS inhibited DOX (1 μM)-induced cytotoxicity in a concentration-dependent manner. Hoechst 33258 staining showed that GS significantly reduced DOX-induced apoptosis and cell death. Using GS at a dose of 10–30 μM significantly reduced intracellular ROS and the formation of MDA in the supernatant of DOX-treated H9C2 cells and suppressed caspase-3 activity to reference levels. In immunoblot analysis, pretreatment using GS significantly reversed DOX-induced decrease of PARP, caspase-3 and bcl-2, and increase of bax, cytochrome C release, cleaved-PARP and cleaved-caspase-3. In addition, the properties of DOX-induced cancer cell (DLD-1 cells) death did not interfere when combined GS and DOX.

Conclusion

These data provide considerable evidence that GS could serve as a novel cardioprotective agent against DOX-induced cardiotoxicity.

Keywords:
Guggulsterone; Doxorubicin; Cardiotoxicity; Cytokines; Reactive oxygen species