A Major Green Tea Component, (−)-Epigallocatechin-3-gallate, Ameliorates Doxorubicin-Mediated Cardiotoxicity in Cardiomyocytes of Neonatal Rats

Li, Wenjuan; Nie, Shaoping; Xie, Mingyong; Chen, Yi; Li, Chang; Zhang, Hui

doi:10.1021/jf101277t

Cited by 49 publications

(30 citation statements)

References 32 publications

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“…16 Other studies emphasize EGCG's antioxidant properties by demonstrating cardioprotection against doxorubicin, an anthracyline aminoglycoside, by attenuating ROS production and increasing expression of endogenous antioxidant enzymes. 17,18 In the present study, co-administration of gentamicin with atRA potentiated hair cell loss and death.…”

Section: Discussionsupporting

confidence: 58%

Role of STAT1 and Oxidative Stress in Gentamicin-Induced Hair Cell Death in Organ of Corti

Jiang

Ray

Rybak³

et al. 2016

Otology &Amp; Neurotology

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Rationale Oxidative stress plays a critical role in gentamicin-induced hair cell death. Prior work has implicated the cytoplasmic transcription factor STAT1 as a potential mediator of drug-induced ototoxicity, but role in aminoglycosides is largely unknown. This study investigated aminoglycosides-induced cell death, exploring contributions of reactive oxygen species and STAT1 pathway in injury and protection. Methods Neonatal murine organ of Corti explants from 2-3 day postnatal pups (n=96) were treated with gentamicin at (4 μΜ, 50 μΜ) for 4-72 hours, with/without protectants. Effects on STAT1 pathway and gentamicin-induced hair cell death were measured with 50 μΜ Epigallocatechin Gallate (EGCG, a STAT1 inhibitor) and all-trans retinoic acid (atRA, a STAT1 activator). Hair cell morphology was evaluated and hair cell loss was quantified with cytocochleograms. Mitochondrial membrane potential was assayed and superoxide generation and suppression was measured with dihydroethidium (DHE) staining. Results Co-administration of 50 μΜ EGCG conferred protection from 4 μΜ gentamicin toxicity (p < 0.001), whereas atRA potentiated gentamicin-induced hair cell death (p<.001). On immunohistochemistry, STAT1 phosphorylation at theserine 727 (Ser727) residues was increased at 72 hours with 4 μΜ gentamicin. With administration of 50 μΜ gentamicin, there was activation of STAT1 Tyr701 at 4 hours and STAT1 Ser727 at 16 hours. Gentamicin dissipated mitochondrial membrane potentials, and EGCG attenuated gentamicin-induced oxidative stress at 72 hours. Conclusion EGCG protected outer hair cells from gentamicin toxicity in a cochlear explant model, with the underlying mechanism involving both reactive oxygen species (ROS) suppression and STAT1 inhibition.

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Section: Discussionsupporting

confidence: 58%

Role of STAT1 and Oxidative Stress in Gentamicin-Induced Hair Cell Death in Organ of Corti

Jiang

Ray

Rybak³

et al. 2016

Otology &Amp; Neurotology

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“…Decreased ROS and MDA levels together with increased expression and activity of antioxidant enzymes showed that induction of the antioxidant defense contributed to the protective effect. 44,45 Moreover, EGCG was shown to improve Ca 2þ handling in DOX-treated cells. 45 Hence, this green tea polyphenol may reverse DOX-induced intracellular Ca 2þ depletion and contribute to the maintenance of contractile function.…”

Section: Cardiotoxicitymentioning

confidence: 99%

Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy

et al. 2013

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s u m m a r yBackground & aims: Green tea catechins, especially epigallocatechin-3-gallate (EGCG), have been associated with cancer prevention and treatment. This has resulted in an increased number of studies evaluating the effects derived from the use of this compound in combination with chemo/radiotherapy. This review aims at compiling latest literature on this subject. Methods: Keywords including EGCG, cancer, chemotherapy, radiotherapy and side effects, were searched using PubMed and ScienceDirect databases to identify, analyze, and summarize the research literature on this topic. Most of the studies on this subject up to date are preclinical. Relevance of the findings, impact factor, and date of publication were critical parameters for the studies to be included in the review. Results: Additive and synergistic effects of EGCG when combined with conventional cancer therapies have been proposed, and its anti-inflammatory and antioxidant activities have been related to amelioration of cancer therapy side effects. However, antagonistic interactions with certain anticancer drugs might limit its clinical use. Conclusions: The use of EGCG could enhance the effect of conventional cancer therapies through additive or synergistic effects as well as through amelioration of deleterious side effects. Further research, especially at the clinical level, is needed to ascertain the potential role of EGCG as adjuvant in cancer therapy.

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“…Various in vivo studies have confirmed that EGCG mitigates doxorubicin-induced cardiotoxicity by suppressing oxidative stress (60–63). The oxygen free radical scavenging ability of EGCG has been demonstrated to protect cardiomyocytes from doxorubicin-mediated cardiotoxicity according to histopathological analysis (64).…”

Section: Discussionmentioning

confidence: 99%

Anti-proliferative activity of epigallocatechin-3-gallate and silibinin on soft tissue sarcoma cells

Harati¹,

Behr²,

Wallner³

et al. 2016

Molecular Medicine Reports

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Disseminated soft tissue sarcomas (STS) present a therapeutic dilemma. The first-line cytostatic doxorubicin demonstrates a response rate of 30% and is not suitable for elderly patients with underlying cardiac disease, due to its cardiotoxicity. Well-tolerated alternative treatment options, particularly in palliative situations, are rare. Therefore, the present study assessed the anti-proliferative effects of the natural compounds epigallocatechin-3-gallate (EGCG), silibinin and noscapine on STS cells. A total of eight different human STS cell lines were used in the study: Fibrosarcoma (HT1080), liposarcoma (SW872, T778 and MLS-402), synovial sarcoma (SW982, SYO1 and 1273) and pleomorphic sarcoma (U2197). Cell proliferation and viability were analysed by 5-bromo-2′-deoxyuridine and MTT assays and real-time cell analysis (RTCA). RTCA indicated that noscapine did not exhibit any inhibitory effects. By contrast, EGCG decreased proliferation and viability of all cell lines except for the 1273 synovial sarcoma cell line. Silibinin exhibited anti-proliferative effects on all synovial sarcoma, liposarcoma and fibrosarcoma cell lines. Liposarcoma cell lines responded particularly well to EGCG while synovial sarcoma cell lines were more sensitive to silibinin. In conclusion, the green tea polyphenol EGCG and the natural flavonoid silibinin from milk thistle suppressed the proliferation and viability of liposarcoma, synovial sarcoma and fibrosarcoma cells. These compounds are therefore potential candidates as mild therapeutic options for patients that are not suitable for doxorubicin-based chemotherapy and require palliative treatment. The findings from the present study provide evidence to support in vivo trials assessing the effect of these natural compounds on solid sarcomas.

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A Major Green Tea Component, (−)-Epigallocatechin-3-gallate, Ameliorates Doxorubicin-Mediated Cardiotoxicity in Cardiomyocytes of Neonatal Rats

Cited by 49 publications

References 32 publications

Role of STAT1 and Oxidative Stress in Gentamicin-Induced Hair Cell Death in Organ of Corti

Role of STAT1 and Oxidative Stress in Gentamicin-Induced Hair Cell Death in Organ of Corti

Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy

Anti-proliferative activity of epigallocatechin-3-gallate and silibinin on soft tissue sarcoma cells

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