Downregulation of CUEDC2 prevents doxorubicin‑induced cardiotoxicity in H9c2 cells

Zhang, Xianpu; Li, Jiaojiao; Yao, Cheng; Yi, Jianguang; Liu, Xin; Cheng, Wei

doi:10.3892/mmr.2018.9072

Cited by 6 publications

(6 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results are consistent with a study by Zhang et al showing that Dox induced cell damage in a dose-and time-dependent manner. Dox (5 μM) caused about 30% reduction in H9c2 cell viability after incubation for 24 h [20], which is similar to our data. By contrast, Dallons et al showed Dox (1-50 μM) had no effect on cell viability after incubation for 4 h, whereas Dox (1 μM) showed 60% reduction in cell viability after 24 h treatment when cell viability was measured by crystal violet assay [21].…”

Section: Dox Induced H9c2 Cell Damage By Increasing Intracellular and Mitochondrial Rossupporting

confidence: 91%

“…Dox is a powerful chemotherapeutic drug and widely used in solid cancer treatment [19]. Dox usage is limited due to induction of irreversible cardiotoxicity [1,20]. This damage is characterized by cardiac cell apoptosis or necrosis which can lead to cardiomyopathy [21].…”

Section: Dox Induced H9c2 Cell Damage By Increasing Intracellular and Mitochondrial Rosmentioning

confidence: 99%

“…In consequence, increased ROS levels in mitochondria lead to membrane potential collapse, ATP production decrease, lipid peroxidation, cytochrome C release and mitochondrial DNA damage [1,20]. A large amount studies have confirmed that Dox induces apoptosis in cardiomyocytes by increasing cytochrome C and caspase 3 and 9 activity [1,20,21].…”

Section: Dox Induced H9c2 Cell Damage By Increasing Intracellular and Mitochondrial Rosmentioning

confidence: 99%

See 2 more Smart Citations

Mitochondrial targeted antioxidants, mitoquinone and SKQ1, not vitamin C, mitigate doxorubicin-induced damage in H9c2 myoblast: pretreatment vs. co-treatment

Sacks

Onal

Martorana

et al. 2021

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

Background Preconditioning of the heart ameliorates doxorubicin (Dox)-induced cardiotoxicity. We tested whether pretreating cardiomyocytes by mitochondrial-targeted antioxidants, mitoquinone (MitoQ) or SKQ1, would provide better protection against Dox than co-treatment. Methods We investigated the dose-response relationship of MitoQ, SKQ1, and vitamin C on Dox-induced damage on H9c2 cardiomyoblasts when drugs were given concurrently with Dox (e.g., co-treatment) or 24 h prior to Dox (e.g., pretreatment). Moreover, their effects on intracellular and mitochondrial oxidative stress were evaluated by 2,7-dichlorofluorescin diacetate and MitoSOX, respectively. Results Dox (0.5–50 μM, n = 6) dose-dependently reduced cell viability. By contrast, co-treatment of MitoQ (0.05–10 μM, n = 6) and SKQ1 (0.05–10 μM, n = 6), but not vitamin C (1–2000 μM, n = 3), significantly improved cell viability only at intermediate doses (0.5–1 μM). MitoQ (1 μM) and SKQ1 (1 μM) significantly increased cell viability to 1.79 ± 0.12 and 1.59 ± 0.08 relative to Dox alone, respectively (both p < 0.05). Interestingly, when given as pretreatment, only higher doses of MitoQ (2.5 μM, n = 9) and SKQ1 (5 μM, n = 7) showed maximal protection and improved cell viability to 2.19 ± 0.13 and 1.65 ± 0.07 relative to Dox alone, respectively (both p < 0.01), which was better than that of co-treatment. Moreover, the protective effects were attributed to the significant reduction in Dox-induced intracellular and mitochondrial oxidative stress. Conclusion The data suggest that MitoQ and SKQ1, but not vitamin C, mitigated DOX-induced damage. Moreover, MitoQ pretreatment showed significantly higher cardioprotection than its co-treatment and SKQ1, which may be due to its better antioxidant effects.

show abstract

Section: Dox Induced H9c2 Cell Damage By Increasing Intracellular and Mitochondrial Rossupporting

confidence: 91%

Section: Dox Induced H9c2 Cell Damage By Increasing Intracellular and Mitochondrial Rosmentioning

confidence: 99%

Section: Dox Induced H9c2 Cell Damage By Increasing Intracellular and Mitochondrial Rosmentioning

confidence: 99%

See 1 more Smart Citation

Mitochondrial targeted antioxidants, mitoquinone and SKQ1, not vitamin C, mitigate doxorubicin-induced damage in H9c2 myoblast: pretreatment vs. co-treatment

Sacks

Onal

Martorana

et al. 2021

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

show abstract

“…Foxo signaling is important for the regulation of cardiomyocyte development and survival. Doxorubicin has been shown to induce cardiomyocyte apoptosis and atrophy through CDK2-mediated activation of FOXO1 signaling [ 43 ], while overexpression of Foxo3A attenuates AIC by inhibiting MIEF2 and mitochondrial disintegration in cardiomyocytes [ 44 ], and activation of FOXO3A signaling reduces anthracycline-induced apoptosis in rat cardiomyocytes [ 45 ], indicating the diversity of FOXO signal in cardiomyocytes. In addition, PI3K-AKT activation was found to upregulate FOXO3A signaling to antagonize AIC [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective Mechanism and Active Compounds of Folium Ginkgo on Adriamycin-Induced Cardiotoxicity: A Network Pharmacology Study

Sun

Zhu

et al. 2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

Objective. To investigate the mechanism of Folium Ginkgo (FG) against adriamycin-induced cardiotoxicity (AIC) through a network pharmacology approach. Methods. Active ingredients of FG were screened by TCMSP, and the targets of active ingredient were collected by Genclip3 and HERB databases. AIC-related target genes were predicted by Genecards, OMIM, and CTD databases. Protein-protein interaction (PPI) network was constructed by STRING platform and imported into Cytoscape software to construct the FG-active ingredients-targets-AIC network, and CytoNCA plug-in was used to analyze and identify the core target genes. The Metascape platform was used for transcription factor, GO and signaling pathway enrichment analysis. Results. 27 active ingredients of FG and 1846 potential targets were obtained and 358 AIC target genes were retrieved. The intersection of FG and AIC targets resulted in 218 target genes involved in FG action. The top 5 active ingredients with most targets were quercetin, luteolin, kaempferol, isorhamnetin, and sesamin. After constructing the FG-active ingredients-targets-AIC network, CytoNCA analysis yielded 51 core targets, of which the top ranked target was STAT3. Ninety important transcription factors were enriched by transcription factor enrichment analysis, including RELA, TP53, NFKB1, SP1, JUN, STAT3, etc. The results of GO enrichment analysis showed that the effective active ingredient targets of FG were involved in apoptotic signaling, response to growth factor, cellular response to chemical stress, reactive oxygen species metabolic process, etc. The signaling pathway enrichment analysis showed that there were many signaling pathways involved in AIC, mainly including pathways in cancer, FOXO signaling pathway, AGE-RAGE signaling pathway in diabetic complications, signaling by interleukins, and PI3K-AKT signaling pathway,. Conclusions. The study based on a network pharmacology approach demonstrates that the possible mechanisms of FG against AIC are the involvement of multicomponents, multitargets, and multipathways, and STAT3 may be a key target. Further experiments are needed to verify the results.

show abstract

“…Lipid peroxidation was evaluated by the Stuart et al method by estimating the malondialdehyde (MDA) levels . Nitric oxide (NO) level was assessed by the Singh et al method …”

Section: Methodsmentioning

confidence: 99%

Ameliorative effect of rosiglitazone, a peroxisome proliferator gamma agonist on adriamycin‐induced cardio toxicity via suppressing oxidative stress and apoptosis

Zhang

et al. 2019

IUBMB Life

View full text Add to dashboard Cite

We investigated the rosiglitazone (RSG) effect on adriamycin (ADM)‐induced cardio toxicity in experimental animals. Forty adult Wistar male rats were separated into four groups as follows: normal control; RSG (10 mg/kg)‐treated; ADM (10 mg/kg)‐administered; and ADM (10 mg/kg) + RSG (10 mg/kg)‐treated. Serum lipid level, different biochemical biomarkers, histological analysis, and nuclear factor erythroid 2‐related factor/heme oxygenase‐1 (Nrf2/HO‐1), Caspase 3, B‐cell lymphoma 2 (Bcl‐2), and Bax gene expression were assessed in serum and cardiac tissue samples. Our results show that RSG treatment in ADM‐administered animals significantly diminished low‐density lipoprotein cholesterol, triglyceride, and total cholesterol, and increases high‐density lipoprotein cholesterol (HDL‐c) in comparison with the ADM group. RSG treatment reduced the effect of ADM administration on cardiac dysfunction markers such as cardiac troponin T Creatine Kinase‐MB, aspartate aminotransferase, and lactate dehydrogenase, showing the amelioration of cardio toxicity in ADM‐administered rats. Additionally, RSG treatment significantly decreased the level of malondialdehyde and nitric oxide in cardiovascular tissue. RSG‐treated rats in combination with ADM likewise showed a significant increase in reduced glutathione, superoxide dismutase, catalase content, and the activity of glutathione peroxidase (GPx) as compared with ADM group. Moreover, RSG treatment in ADM rats significantly increased an Nrf2 and HO‐1 expression in comparison with ADM group. While in apoptosis parameters, RSG treatment in ADM rats significantly diminished a cleaved caspase‐3 and Bax expression as well as expanded Bcl‐2 expression when contrasted with ADM group of rats. In conclusion, RSG is capable of protecting heart toxicity in ADM‐treated animals through defensive effects on oxidative stress and biochemical markers.

show abstract

Downregulation of CUEDC2 prevents doxorubicin‑induced cardiotoxicity in H9c2 cells

Cited by 6 publications

References 42 publications

Mitochondrial targeted antioxidants, mitoquinone and SKQ1, not vitamin C, mitigate doxorubicin-induced damage in H9c2 myoblast: pretreatment vs. co-treatment

Mitochondrial targeted antioxidants, mitoquinone and SKQ1, not vitamin C, mitigate doxorubicin-induced damage in H9c2 myoblast: pretreatment vs. co-treatment

Cardioprotective Mechanism and Active Compounds of Folium Ginkgo on Adriamycin-Induced Cardiotoxicity: A Network Pharmacology Study

Ameliorative effect of rosiglitazone, a peroxisome proliferator gamma agonist on adriamycin‐induced cardio toxicity via suppressing oxidative stress and apoptosis

Contact Info

Product

Resources

About