Plantainoside D protects adriamycin-induced apoptosis in H9c2 cardiac muscle cells via the inhibition of ROS generation and NF-κB activation

Kim, Do‐Sung; Woo, Eun‐Rhan; Chae, Soo‐Wan; Ha, Ki-Chan; Lee, Geum-Hwa; Hong, Seong‐Tshool; Kwon, Dae-Young; Kim, Myung-Sunny; Jung, Yong‐Keun; Kim, Hyung-Min; Kim, Hye-Kyung; Kim, Hyung‐Ryong; Chae, Han‐Jung

doi:10.1016/j.lfs.2006.09.019

Cited by 59 publications

(41 citation statements)

References 27 publications

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“…Cardiomyocytes are well known to have lower levels of superoxide anion and hydrogen peroxide-detoxifying enzymes compared to other cell types, hence, ROSinduced oxidative stress is amplified [42]. Given this mechanism of action, there has been intense investigation into the potential of free radical scavengers, including natural antioxidants to ameliorate the side-effects of doxorubicin [43][44][45][46][47][48]. Among the various compounds, the potent immunosuppressant rapamycin shows promising effects in inhibiting hypertrophic responses and senescence [43][44][45][46][47][48][49][50][51].…”

Section: Discussionmentioning

confidence: 99%

Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes

Ververis

Rodd

Tang

et al. 2011

Cell. Mol. Life Sci.

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Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutics with suberoylanilide hydroxamic acid (Vorinostat) and depsipeptide (Romidepsin) already being approved for clinical use. Numerous studies have identified that histone deacetylase inhibitors will be most effective in the clinic when used in combination with conventional cancer therapies such as ionizing radiation and chemotherapeutic agents. One promising combination, particularly for hematologic malignancies, involves the use of histone deacetylase inhibitors with the anthracycline, doxorubicin. However, we previously identified that trichostatin A can potentiate doxorubicin-induced hypertrophy, the dose-limiting side-effect of the anthracycline, in cardiac myocytes. Here we have the extended the earlier studies and evaluated the effects of combinations of the histone deacetylase inhibitors, trichostatin A, valproic acid and sodium butyrate on doxorubicin-induced DNA double-strand breaks in cardiomyocytes. Using γH2AX as a molecular marker for the DNA lesions, we identified that all of the broad-spectrum histone deacetylase inhibitors tested augment doxorubicin-induced DNA damage. Furthermore, it is evident from the fluorescence photomicrographs of stained nuclei that the histone deacetylase inhibitors also augment doxorubicin-induced hypertrophy. These observations highlight the importance of investigating potential side-effects, in relevant model systems, which may be associated with emerging combination therapies for cancer.

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Section: Discussionmentioning

confidence: 99%

Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes

Ververis

Rodd

Tang

et al. 2011

Cell. Mol. Life Sci.

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“…On the other hand, this same cell line has been used as a model to investigate the protective effect of several compounds against Dox-induced cardiotoxicity. Among such compounds, carvedilol (Spallarossa et al 2004), rosmarinic acid , plantainoside D (Kim et al 2007), or thrombopoietin (Li et al 2006) are particular examples.…”

Section: Discussionmentioning

confidence: 99%

Morphological alterations induced by doxorubicin on H9c2 myoblasts: nuclear, mitochondrial, and cytoskeletal targets

et al. 2008

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Doxorubicin (Dox) is a very potent antineoplastic agent used against several types of cancer, despite a cumulative cardiomyopathy that reduces the therapeutic index for treatment. H9c2 myoblast cells have been used as an in vitro model to study biochemical alterations induced by Dox treatment on cardiomyocyte cells. Despite the extensive work already published, few data are available regarding morphological alterations of H9c2 cells during Dox treatment. The purpose of the present work was to evaluate Doxinduced morphological alterations in H9c2 myoblasts, focusing especially on the nuclei, mitochondria, and structural fibrous proteins. Treatment of H9c2 cell with low concentrations of Dox causes alterations in fibrous structural proteins including the nuclear lamina and sarcomeric cardiac myosin, as well as mitochondrial depolarization and fragmentation, membrane blebbing with cell shape changes, and phosphatidylserine externalization. For higher Dox concentrations, more profound alterations are evident, including nuclear swelling with disruption of nuclear membrane structure, mitochondrial swelling, and extensive cytoplasm vacuolization. The results obtained indicate that Dox causes morphological alterations in mitochondrial, nuclear, and fibrous protein structures in H9c2 cells, which are dependent on the drug concentration. Data obtained with the present study allow for a better characterization of the effects of Dox on H9c2 myoblasts, used as a model to study Dox-induced cardiotoxicity. The results obtained also provide new and previously unknown targets that can contribute to understand the mechanisms involved in the cardiotoxicity of Dox.

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“…As discussed above, Doxorubicin-induced cardiotoxicity is a complex multifactorial process, in which mitochondrial ROS production plays a critical role [29][30][31][32][33][34]. ROS production, on the other hand, has been reported as a strong AMPK activator [31,35,36], and so the possible involvement of ROS production in Doxorubicin-induced AMPK activation was next tested.…”

Section: Ampk Activation Contributes To Doxorubicin-induced H9c2 Cellmentioning

confidence: 99%

“…ROS production, on the other hand, has been reported as a strong AMPK activator [31,35,36], and so the possible involvement of ROS production in Doxorubicin-induced AMPK activation was next tested. As shown in Fig.…”

Section: Ampk Activation Contributes To Doxorubicin-induced H9c2 Cellmentioning

confidence: 99%

Activation of AMP-Activated Protein Kinase Contributes to Doxorubicin-Induced Cell Death and Apoptosis in Cultured Myocardial H9c2 Cells

Chen

et al. 2011

Cell Biochem Biophys

104

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Despite its potent antitumor effect, clinical use of Doxorubicin is limited because of serious side effects including myocardial toxicity. Understanding the cellular mechanism involved in this process in a better manner is beneficial for optimizing Doxorubicin treatment. In the current study, the authors focus on the AMP-activated protein kinase (AMPK) in the said process. In this study, the authors discovered for the first time that Doxorubicin induces AMPK activation in cultured rat embryonic ventricular myocardial H9c2 cells. Reactive oxygen species (ROS)-dependent LKB1 activation serves as the upstream signal for AMPK activation by Doxorubicin. Evidence in support of the activation of AMPK contributing to Doxorubicin-induced H9c2 cell death/apoptosis--probably by modulating multiple downstream signal targets, including regulating JNK, p53, and inhibiting mTORC1--is provided in this article.

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Plantainoside D protects adriamycin-induced apoptosis in H9c2 cardiac muscle cells via the inhibition of ROS generation and NF-κB activation

Cited by 59 publications

References 27 publications

Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes

Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes

Morphological alterations induced by doxorubicin on H9c2 myoblasts: nuclear, mitochondrial, and cytoskeletal targets

Activation of AMP-Activated Protein Kinase Contributes to Doxorubicin-Induced Cell Death and Apoptosis in Cultured Myocardial H9c2 Cells

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