Abstract
BackgroundDoxorubicin (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.MethodsIn 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.ResultsThe 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.ConclusionThese data provide considerable evidence that GS could serve as a novel cardioprotective agent against DOX-induced cardiotoxicity.
Highlights
Doxorubicin (DOX) is an effective antineoplastic drug; clinical use of DOX is limited by its dose-dependent cardiotoxicity
Previous studies have suggested that one mechanism responsible for DOX cardiotoxicity is the formation of reactive oxygen species (ROS) [5,6], which can harm membrane lipids and other cellular components, leading to cardiomyocyte apoptosis and death [7]
GS protected H9C2 cells from DOX-induced cell death To determine GS concentrations prevented in DOXinduced cytotoxicity, we examined the preventive abilities of GS in H9C2 cells at different concentrations
Summary
Doxorubicin (DOX) is an effective antineoplastic drug; clinical use of DOX is limited by its dose-dependent cardiotoxicity. 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. Despite the efficacy of DOX, its use has been limited by the dose-dependent cardiotoxicity associated with acute and chronic treatments in anticancer therapy [1,2,3] Both acute and chronic DOX-induced cardiotoxicity may cause cardiac dysfunction or cardiomyopathy, and may lead to rigorous heart failure and death [3,4]. During a 10-year period, myrrh was examined to treat various conditions, such as rheumatism, atherosclerosis, hypercholesterolemia, and obesity [16] Both GS isomers were demonstrated to suppress LPS-induced inflammation by inhibiting IκB-α degradation and NF-κB activation [17,18]. This study is the first to evaluate the protective effects of GS to determine the preliminary mechanisms of defending against DOX-induced cytotoxicity in H9C2 cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
