Search

Resveratrol is a polyphenolic compound found in wine, which is mainly produced by the grapevine and exerts chemopreventive effects against hepatocellular carcinoma. However, the underlying molecular mechanisms have remained to be fully elucidated. The present study assessed whether resveratrol-induced apoptosis was mediated via the activation of the forkhead box O3a (FoxO3a) transcription factor. It was demonstrated that resveratrol treatment induced apoptosis in HepG2 cells, and that this pro-apoptotic effect was accompanied with increases in the expression of apoptotic protein Bim. Following resveratrol treatment, Akt-mediated phosphorylation of FoxO3a was observed to be diminished in HepG2 cells. Furthermore, resveratrol enhanced the nuclear levels of FoxO3a and mediated neuronal death via Bim. The present study demonstrated that resveratrol induced apoptosis in HepG2 cells through activation of the transcription factor FoxO3a and increasing the expression of Bim protein. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is an efficient drug used in cancer therapy; however, it has severe cardiotoxic side effects. The aim of the present study was to investigate the effects of resveratrol on the adenosine monophosphate-activated protein kinase (AMPK)/P53 pathway in mediating DOX-induced cytotoxicity. H9c2 cells were exposed to 5 μM DOX for 24 h to establish a model of DOX-induced cardiotoxicity. DOX administration ampli?ed P53 and B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) expression and decreased Bcl-2 expression in H9c2 cells. Resveratrol increased the cell viability and decreased the apoptotic rate. In addition, resveratrol markedly increased the phosphorylation of AMPK. Of note, resveratrol protected against DOX-induced increases of P53 and Bax and also prevented the downregulation of Bcl-2 in H9c2 cells. Furthermore, AMPK inhibitor Compound C abolished the protective effects of resveratrol. The results of the present study therefore indicated that resveratrol protected H9c2 cells from DOX-induced apoptosis via the AMPK/P53 pathway. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a widely used chemotherapeutic agent, which can give rise to severe cardiotoxicity, limiting its clinical use. Preliminary evidence suggests that hydrogen sulfide (H2S) may exert protective effects on DOX-induced cardiotoxicity. Therefore, the aim of the present study was to investigate whether peroxiredoxin III is involved in the cardioprotection of H2S against DOX-induced cardiotoxicity. The results demonstrated that DOX not only markedly induced injuries, including cytotoxicity and apoptosis, it also increased the expression levels of peroxiredoxin III. Notably, pretreatment with sodium hydrosulfide significantly attenuated the DOX-induced decrease in cell viability and increase in apoptosis, and also reversed the increased expression levels of peroxiredoxin III in H9c2 cardiomyocytes. In addition, pretreatment of the H9c2 cells with N-acetyl-L-cysteine, a scavenger of reactive oxygen species, prior to exposure to DOX markedly decreased the expression levels of peroxiredoxin III. In conclusion, the results of the present study suggested that exogenous H2S attenuates DOX-induced cardiotoxicity by inhibiting the expression of peroxiredoxin III in H9c2 cells. In the present study, the apoptosis of H9c2 cardiomyocytes was assessed using an methyl thiazolyl tetrazolium assay and Hoechst staining. The levels of Prx III and cystathionine-γ- lyase were examined by western blotting. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a potent and available antitumor therapeutic agent; however, its clinical application is limited due to its cardiotoxicity. Preliminary evidence suggests that hydrogen sulfide (H2S) may exert protective effects on DOX-induced cardiotoxicity. Therefore, the aim of the present study was to investigate whether the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway is involved in the cardioprotection of H2S against DOX-induced cardiotoxicity. The present study demonstrated that pretreatment with sodium hydrosulfide (NaHS; a donor of H2S) prior to DOX exposure attenuated the decreased cell viability, the increased apoptosis rate and the intracellular accumulation of reactive oxygen species (ROS) in H9c2 cardiac myocytes. Exposure of H9c2 cardiac myocytes to DOX upregulated the expression levels of phosphorylated ERK1/2, which had been reduced by pretreatment with NaHS or N-acetyl-L-cysteine, a ROS scavenger. In addition, H2S upregulated the anti-apoptotic protein, Bcl-2 and downregulated the pro-apoptotic protein, Bax. Notably, U0126, a selective inhibitor of ERK1/2, was observed to mimic the above-mentioned cytoprotective activity of H2S. In conclusion, these findings indicate that H2S attenuates DOX-induced cardiotoxicity by inhibiting ROS-mediated activation of ERK1/2 in H9c2 cardiac myocytes. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is an efficient drug used in cancer therapy; however, it produces reactive oxygen species (ROS) that induce severe cytotoxicity, limiting its clinical application. The aim of the present study was to investigate the role of peroxiredoxin III (Prx III) in DOX-induced H9c2 cell injuries. Following DOX treatment, the expression of phosphorylated-FoxO3a (p-FoxO3a) was decreased and Prx III expression was increased in H9c2 cells. In order to detect whether oxidative stress was involved in the induction of Prx III expression by FoxO3a, exogenous H2O2 was used to induce oxidative stress in the H9c2 cells. Apoptosis of H9c2 cardiomyocytes was assessed using methyl thiazolyl tetrazolium assay and Hoechst staining. The levels of Prx III and p-FoxO3a were evaluated using western blot analysis. As expected, H2O2 was found to mimic the effect of DOX, decreasing the expression of p-FoxO3a and increasing the expression of Prx III. In addition, the study evaluated whether the transcription factor FoxO3a was essential for the expression of Prx III. Pretreatment of H9c2 cells with N-acetyl-L-cysteine (NAC), a scavenger of ROS, prior to exposure to DOX dramatically increased the phosphorylation of FoxO3a and led to a marked reduction in Prx III expression in the H9c2 cells. In conclusion, the results of the current study suggest that FoxO3a mediates the expression of Prx III in DOX-induced injuries. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a potent and currently available antitumor therapeutic agent; however, its clinical application is limited by the occurrence of cardiotoxicity. Preliminary evidence indicates that hydrogen sulfide (H2S) may exert protective effects against DOX cardiotoxicity. Therefore, the aim of the present study was to investigate whether calreticulin (CRT) is involved in the cardioprotection of H2S against DOX-induced cardiotoxicity. DOX was observed to markedly induce injuries, including cytotoxicity and apoptosis, and also enhance the expression level of CRT. Notably, pretreatment of H9c2 cells with sodium hydrosulfide (a donor of H2S) significantly attenuated the decreased cell viability, the increased apoptosis rate and the increased expression level of CRT in H9c2 cells. In addition, pretreatment of H9c2 cells with N-acetyl-L-cysteine, a scavenger of reactive oxygen species (ROS) prior to exposure to DOX, markedly decreased the expression of CRT. These results indicate that exogenous H2S attenuates DOX-induced cardiotoxicity by inhibiting CRT expression in H9c2 cardiac cells. [ABSTRACT FROM AUTHOR]