Sun, Lei’s team published research in International Journal of Molecular Medicine in 2022-02-28 | 347174-05-4

International Journal of Molecular Medicine published new progress about Antioxidant enzymes Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate.

Sun, Lei; Wang, Hua; Yu, Shanshan; Zhang, Lin; Jiang, Jue; Zhou, Qi published the artcile< Herceptin induces ferroptosis and mitochondrial dysfunction in H9c2 cells>, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate, the main research area is herceptin ferroptosis mitochondrial dysfunction heart failure; Herceptin; cardiotoxicity; ferroptosis; mitochondrial dysfunction.

Ferroptosis has been previously implicated in the pathol. progression of cardiomyopathy. Herceptin (trastuzumab), which targets HER2, is commonly applied for the treatment of HER2+ breast cancer. However, its clin. use is limited by its cardiotoxicity. Therefore, the present study aimed to investigate if targeting ferroptosis could protect against Herceptin-induced heart failure in an in vitro model of H9c2 cells after treatment of Herceptin, Herceptin + ferroptosis inhibitor ferrostatin-1 (Fer-1) or Herceptin + Deferoxamine. H9c2 cell viability was measured by MTT assay. Reactive oxygen species (ROS) levels were detected by measuring the fluorescence of DCFH-DA-A and MitoSOX Red. Glutathione (GSH)/oxidized glutathione (GSSG) ratio was measured using the GSH/GSSG Ratio Detection Assay kit. Mitochondrial membrane potential and ATP content were evaluated by JC-1 staining and bioluminescent assay kits, resp. Protein expressions of glutathione peroxidase 4, recombinant solute carrier family 7 member 11, mitochondrial optic atrophy1-1/2, mitofusin, Acyl-CoA synthetase long chain family member 4, cytochrome c, voltage-dependent anion-selective channel, dynamin-related protein, mitochondrial fission 1 protein and mitochondrial ferritin were evaluated by western blotting. It was found that Herceptin reduced H9c2 cell viability while increasing intracellular and mitochondrial ROS levels in a dose- and time-dependent manner. Furthermore, Herceptin decreased glutathione peroxidase (GPX) protein expression and the GSH/GSSG ratio in H9c2 cells in a dose- and time-dependent manner. The Fer-1 abolished this Herceptin-induced reduction in cell viability, GSH/GSSG ratio, mitochondrial membrane potential and ATP content. Fer-1 also reversed the suppressive effects of Herceptin on the protein expression levels of GPX4, recombinant solute carrier family 7 member 11, mitochondrial optic atrophy1-1/2 and mitofusin in H9c2 cells. Subsequently, Fer-1 was found to reverse the Herceptin-induced increase in mitochondrial ROS and iron levels in H9c2 cells, as well as the increased protein expression levels of Acyl-CoA synthetase long chain family member 4, cytochrome c, voltage-dependent anion-selective channel, dynamin-related protein, mitochondrial fission 1 protein and mitochondrial ferritin in H9c2 cells. However, compared with deferoxamine, an iron chelator, the effects of Fer-1 were less effective. Collectively, these findings provided insights into the pathogenic mechanism that underlie Herceptin-induced cardiomyopathy, which potentially provides a novel therapeutic target for the prevention of cardiotoxicity in HER2+ breast cancer treatment.

International Journal of Molecular Medicine published new progress about Antioxidant enzymes Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate.

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