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

Wen Ching Wang, Yih Huei Uen, Ming Long Chang, Khoot Peng Cheah, Joe Sharg Li, Wen Yu Yu, Kock Chee Lee, Cheuk Sing Choy, Chien Ming Hu

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number138
JournalBMC Complementary and Alternative Medicine
Volume12
DOIs
Publication statusPublished - Aug 27 2012

Fingerprint

Cardiac Myocytes
Doxorubicin
Wounds and Injuries
Caspase 3
Bisbenzimidazole
Reactive Oxygen Species
L-Lactate Dehydrogenase
In Vitro Techniques
pregna-4,17-diene-3,16-dione
Cell Death
Apoptosis
Staining and Labeling
Cardiotonic Agents
Pathologic Processes
Cytochromes
Antineoplastic Agents
Lipid Peroxidation
Fluorescent Antibody Technique
Western Blotting
Steroids

Keywords

  • Cardiotoxicity
  • Cytokines
  • Doxorubicin
  • Guggulsterone
  • Reactive oxygen species

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

Protective effect of guggulsterone against cardiomyocyte injury induced by doxorubicin in vitro. / Wang, Wen Ching; Uen, Yih Huei; Chang, Ming Long; Cheah, Khoot Peng; Li, Joe Sharg; Yu, Wen Yu; Lee, Kock Chee; Choy, Cheuk Sing; Hu, Chien Ming.

In: BMC Complementary and Alternative Medicine, Vol. 12, 138, 27.08.2012.

Research output: Contribution to journalArticle

Wang, Wen Ching ; Uen, Yih Huei ; Chang, Ming Long ; Cheah, Khoot Peng ; Li, Joe Sharg ; Yu, Wen Yu ; Lee, Kock Chee ; Choy, Cheuk Sing ; Hu, Chien Ming. / Protective effect of guggulsterone against cardiomyocyte injury induced by doxorubicin in vitro. In: BMC Complementary and Alternative Medicine. 2012 ; Vol. 12.
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AU - Chang, Ming Long

AU - Cheah, Khoot Peng

AU - Li, Joe Sharg

AU - Yu, Wen Yu

AU - Lee, Kock Chee

AU - Choy, Cheuk Sing

AU - Hu, Chien Ming

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N2 - 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.

AB - 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.

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