The anti-cancer drug doxorubicin induces substantial epigenetic changes in cultured cardiomyocytes

Hanf, Alina; Oelze, Matthias; Manea, Adrian; Li, Huige; Münzel, Thomas; Daiber, Andreas

doi:10.1016/j.cbi.2019.108834

Cited by 43 publications

(31 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, a recent study using H9c2 cardiac myoblast cells also demonstrated that expression of several histone modifiers was dysregulated in association with downregulation of global acetylation of histone H3 (Table 1). In this study, Hanf et al (47) demonstrated that expression levels of histone deacetylases (SIRT1 and HDAC2) were affected upon DOX treatment. In particular, different isoforms of SIRT1 displayed a contradictory expression level.…”

Section: Histone Modificationmentioning

confidence: 62%

“…Similarly, upregulation of miR-23a (58), miR-34a (61, 62), miR-140 (63), miR-146a (64), and miR-532 (66) were observed either in vitro or in vivo models of DOX-induced cardiotoxicity. Interestingly, upregulation of miR-34a, a well-known tumor suppressive miRNA, could epigenetically suppress SIRT1 (61,62), thus partially explaining the downregulation of this HDAC, by DOX, in the aforementioned study (47).…”

Section: Noncoding Rna Expressionmentioning

confidence: 77%

See 1 more Smart Citation

Review on the Role of Epigenetic Modifications in Doxorubicin-Induced Cardiotoxicity

Kumari

Huang

Chan

2020

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Use of anthracyclines such as doxorubicin (DOX), for the treatment of cancer, is known to induce cardiotoxicity, begetting numerous evaluations of this adverse effect. This review emphasizes the mechanism of how consideration of DOX-induced cardiotoxicity is important for the development of cardioprotective agents. As DOX is involved in mitochondrial dysfunction, enzymes involved in epigenetic modifications that use mitochondrial metabolite as substrate are most likely to be affected. Therefore, this review article focuses on the fact that epigenetic modifications, namely, DNA methylation, histone modifications, and noncoding RNA expression, contribute to DOX-associated cardiotoxicity. Early interventions needed for patients undergoing chemotherapy, to treat or prevent heart failure, would, overall, improve the survival, and quality of life of cancer patients. These epigenetic modifications can either be used as molecular markers for cancer prognosis or represent molecular targets to attenuate DOX-induced cardiotoxicity in cancer patients.

show abstract

Section: Histone Modificationmentioning

confidence: 62%

Section: Noncoding Rna Expressionmentioning

confidence: 77%

Review on the Role of Epigenetic Modifications in Doxorubicin-Induced Cardiotoxicity

Kumari

Huang

Chan

2020

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…Therefore, the genetic or pharmacological inhibition action of HDAC6 in mice has a cardioprotective effect on DOX by restoring the autophagic flux. In another study, Hanf et al proved that DOX treatment affected the expression level of HDAC (SIRT1 and HDAC2) [ 303 ]. Nevertheless, pterostilbene, a natural analog of resveratrol and an antioxidant, was found to reduce cardiotoxicity induced by DOX both in vitro and in vivo [ 304 ].…”

Section: Protective Genes In Cancer Treatment-induced Cardiotoxicimentioning

confidence: 99%

Possible Susceptibility Genes for Intervention against Chemotherapy-Induced Cardiotoxicity

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Recent therapeutic advances have significantly improved the short- and long-term survival rates in patients with heart disease and cancer. Survival in cancer patients may, however, be accompanied by disadvantages, namely, increased rates of cardiovascular events. Chemotherapy-related cardiac dysfunction is an important side effect of anticancer therapy. While advances in cancer treatment have increased patient survival, treatments are associated with cardiovascular complications, including heart failure (HF), arrhythmias, cardiac ischemia, valve disease, pericarditis, and fibrosis of the pericardium and myocardium. The molecular mechanisms of cardiotoxicity caused by cancer treatment have not yet been elucidated, and they may be both varied and complex. By identifying the functional genetic variations responsible for this toxicity, we may be able to improve our understanding of the potential mechanisms and pathways of treatment, paving the way for the development of new therapies to target these toxicities. Data from studies on genetic defects and pharmacological interventions have suggested that many molecules, primarily those regulating oxidative stress, inflammation, autophagy, apoptosis, and metabolism, contribute to the pathogenesis of cardiotoxicity induced by cancer treatment. Here, we review the progress of genetic research in illuminating the molecular mechanisms of cancer treatment-mediated cardiotoxicity and provide insights for the research and development of new therapies to treat or even prevent cardiotoxicity in patients undergoing cancer treatment. The current evidence is not clear about the role of pharmacogenomic screening of susceptible genes. Further studies need to done in chemotherapy-induced cardiotoxicity.

show abstract

“…Additionally, we used the following antibodies for dot blot analysis of blood plasma: interleukin-6 (IL-6, rabbit polyclonal, 1:1000, Abcam, Cambridge, MA, USA), 3-nitrotyrosine (3-NT, rabbit polyclonal, 1:1000, Millipore, Burlington, USA), and 4-hydroxynonenal (4-HNE, goat polyclonal, 1:1000, Sigma-Aldrich). Goat anti-mouse and goat anti-rabbit peroxidase-coupled secondary antibodies (1:10,000, Vector Laboratories, CA, USA) were used for the detection of positive bands along with enhanced chemiluminescence (ECL) development [26]. Equal loading of protein samples in dot blot analysis was ensured by Bradford-based determination of protein concentration and loading of 25 µg of heart or plasma protein to the nitrocellulose membrane in each well.…”

Section: Western Blotting and Dot Blot Analysismentioning

confidence: 99%

Noise-Induced Vascular Dysfunction, Oxidative Stress, and Inflammation Are Improved by Pharmacological Modulation of the NRF2/HO-1 Axis

et al. 2021

Self Cite

View full text Add to dashboard Cite

Vascular oxidative stress, inflammation, and subsequent endothelial dysfunction are consequences of traditional cardiovascular risk factors, all of which contribute to cardiovascular disease. Environmental stressors, such as traffic noise and air pollution, may also facilitate the development and progression of cardiovascular and metabolic diseases. In our previous studies, we investigated the influence of aircraft noise exposure on molecular mechanisms, identifying oxidative stress and inflammation as central players in mediating vascular function. The present study investigates the role of heme oxygenase-1 (HO-1) as an antioxidant response preventing vascular consequences following exposure to aircraft noise. C57BL/6J mice were treated with the HO-1 inducer hemin (25 mg/kg i.p.) or the NRF2 activator dimethyl fumarate (DMF, 20 mg/kg p.o.). During therapy, the animals were exposed to noise at a maximum sound pressure level of 85 dB(A) and a mean sound pressure level of 72 dB(A). Our data showed a marked protective effect of both treatments on animals exposed to noise for 4 days by normalization of arterial hypertension and vascular dysfunction in the noise-exposed groups. We observed a partial normalization of noise-triggered oxidative stress and inflammation by hemin and DMF therapy, which was associated with HO-1 induction. The present study identifies possible new targets for the mitigation of the adverse health effects caused by environmental noise exposure. Since natural dietary constituents can achieve HO-1 and NRF2 induction, these pathways represent promising targets for preventive measures.

show abstract

The anti-cancer drug doxorubicin induces substantial epigenetic changes in cultured cardiomyocytes

Cited by 43 publications

References 101 publications

Review on the Role of Epigenetic Modifications in Doxorubicin-Induced Cardiotoxicity

Review on the Role of Epigenetic Modifications in Doxorubicin-Induced Cardiotoxicity

Possible Susceptibility Genes for Intervention against Chemotherapy-Induced Cardiotoxicity

Noise-Induced Vascular Dysfunction, Oxidative Stress, and Inflammation Are Improved by Pharmacological Modulation of the NRF2/HO-1 Axis

Contact Info

Product

Resources

About