Ng cause of death worldwide for decades. Thus, scientists have actively

Ng cause of death worldwide for decades. Thus, scientists have actively devoted themselves to studying cancer therapeutics. Doxorubicin is an efficient drug used in cancer therapy, but also produces reactive oxygen species (ROS) that induce severe cytotoxicity against heart cells. Quercetin, a plant-derived flavonoid, has been proven to contain potent antioxidant and anti-inflammatory properties. Thus, this in vitro study investigated whether quercetin can decrease doxorubicin-induced cytotoxicity and promote cell repair systems in cardiomyocyte H9C2 cells. Results: Proteomic analysis and a cell biology assay were performed to investigate the quercetin-induced responses. Our data demonstrated that quercetin treatment protects the BAY1217389 biological activity cardiomyocytes in a doxorubicin-induced heart damage model. Quercetin significantly facilitated cell survival by inhibiting cell apoptosis and maintaining cell morphology by rearranging the cytoskeleton. Additionally, 2D-DIGE combined with MALDI-TOF MS analysis indicated that quercetin might stimulate cardiomyocytes to repair damage after treating doxorubicin by modulating metabolic activation, protein folding and cytoskeleton rearrangement. Conclusion: Based on a review of the literature, this study is the first to report detailed protective mechanisms for the action of quercetin against doxorubicin-induced cardiomyocyte toxicity based on in-depth cell biology and proteomic analysis. Keywords: Quercetin, Doxorubicin, Proteomics, DIGE, MALDI-TOF, CardiomyocytesBackground Doxorubicin is a chemotherapy drug, commonly used in various cancer treatments, such as breast cancer, lung cancer and several other carcinoma types [1-3]. The principal mechanism of doxorubicin is chelating DNA, inhibiting topoisomerase II and then producing free radicals to kill cancer cells. Reported side effects of doxorubicin include cardiotoxicity, comprising cardiomyopathy and ultimately fatal congestive heart failure. Because myocardia are particularly sensitive to reactive oxygen species (ROS), cumulative doxorubicin in vivo causes irreversible damage to heart cells, thus restricting clinical use of this drug [4]. Although the specific causal mechanism of doxorubicininduced cardiotoxicity remains largely unclear, most of the evidence has indicated that doxorubicin is reduced to its semiquinone form by a mitochondria electron transport system. The semiquinone subsequently reacts with* Correspondence: [email protected] Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwanoxygen, iron, and hydrogen peroxide to produce ROS Leupeptin (hemisulfate) dose causing cell apoptosis and myocyte damage [5,6]. In addition, global analysis of doxorubicin-induced cellular oxidative stress has indicated that doxorubicin treatment contributes to the over-expression of anti-oxidant proteins such as glutathione reductase and peroxiredoxin in brain cells, lung cells and heart cells [7-9]. Quercetin, a type of polyphenolic compound found in various plant products, possesses anti-oxidant, antiproliferative, anti-inflammatory and anti-histamine properties. Several reports have indicated that quercetin exerts protective effects PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27362935 on various cells, including myocytes, testes, renal cells and liver cells in ischemia and reperfusion injury [10]. A study conducted in 1992 determined that quercetin reduces the oxidative stress caused by ischemia and reperfusion in cardiomyocytes by inhibiting the xanthine dehydrogenase and xanthine oxidase system [11]. Se.Ng cause of death worldwide for decades. Thus, scientists have actively devoted themselves to studying cancer therapeutics. Doxorubicin is an efficient drug used in cancer therapy, but also produces reactive oxygen species (ROS) that induce severe cytotoxicity against heart cells. Quercetin, a plant-derived flavonoid, has been proven to contain potent antioxidant and anti-inflammatory properties. Thus, this in vitro study investigated whether quercetin can decrease doxorubicin-induced cytotoxicity and promote cell repair systems in cardiomyocyte H9C2 cells. Results: Proteomic analysis and a cell biology assay were performed to investigate the quercetin-induced responses. Our data demonstrated that quercetin treatment protects the cardiomyocytes in a doxorubicin-induced heart damage model. Quercetin significantly facilitated cell survival by inhibiting cell apoptosis and maintaining cell morphology by rearranging the cytoskeleton. Additionally, 2D-DIGE combined with MALDI-TOF MS analysis indicated that quercetin might stimulate cardiomyocytes to repair damage after treating doxorubicin by modulating metabolic activation, protein folding and cytoskeleton rearrangement. Conclusion: Based on a review of the literature, this study is the first to report detailed protective mechanisms for the action of quercetin against doxorubicin-induced cardiomyocyte toxicity based on in-depth cell biology and proteomic analysis. Keywords: Quercetin, Doxorubicin, Proteomics, DIGE, MALDI-TOF, CardiomyocytesBackground Doxorubicin is a chemotherapy drug, commonly used in various cancer treatments, such as breast cancer, lung cancer and several other carcinoma types [1-3]. The principal mechanism of doxorubicin is chelating DNA, inhibiting topoisomerase II and then producing free radicals to kill cancer cells. Reported side effects of doxorubicin include cardiotoxicity, comprising cardiomyopathy and ultimately fatal congestive heart failure. Because myocardia are particularly sensitive to reactive oxygen species (ROS), cumulative doxorubicin in vivo causes irreversible damage to heart cells, thus restricting clinical use of this drug [4]. Although the specific causal mechanism of doxorubicininduced cardiotoxicity remains largely unclear, most of the evidence has indicated that doxorubicin is reduced to its semiquinone form by a mitochondria electron transport system. The semiquinone subsequently reacts with* Correspondence: [email protected] Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwanoxygen, iron, and hydrogen peroxide to produce ROS causing cell apoptosis and myocyte damage [5,6]. In addition, global analysis of doxorubicin-induced cellular oxidative stress has indicated that doxorubicin treatment contributes to the over-expression of anti-oxidant proteins such as glutathione reductase and peroxiredoxin in brain cells, lung cells and heart cells [7-9]. Quercetin, a type of polyphenolic compound found in various plant products, possesses anti-oxidant, antiproliferative, anti-inflammatory and anti-histamine properties. Several reports have indicated that quercetin exerts protective effects PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27362935 on various cells, including myocytes, testes, renal cells and liver cells in ischemia and reperfusion injury [10]. A study conducted in 1992 determined that quercetin reduces the oxidative stress caused by ischemia and reperfusion in cardiomyocytes by inhibiting the xanthine dehydrogenase and xanthine oxidase system [11]. Se.