In radiation oncology, ionizing radiation is used to kill cancer cells, in other words, the induction of different types of cell death. To investigate this cellular death and the associated iron accumulation, the transfer, release, and participation of iron after radiation treatment was analyzed. We found that radiation-induced cell death varied in different breast cancer cells and autophagy was induced in MDA-MB-231 and BT549 cells (triple negative breast cancer cell line) rather than in MCF-7 and zr-75 cells. Iron chelator deferoxamine (DFO), the autophagy inhibitor 3MA, silencing of the autophagy-related genes ATG5, and Beclin 1 could decrease radiation induced cell death in MDA-MB-231 cells, while inhibitors of apoptosis such as Z-VAD-FMK, ferroptosis inhibitor ferrostatin-1 (Fer-1), and necroptosis inhibitor Necrostatin-1 showed no change. This suggests the occurrence of autophagic cell death. Furthermore, we found that iron accumulation and iron regulatory proteins, including transferrin (Tf), transferrin receptor (CD71), and Ferritin (FTH), increased after radiation treatment, and the silencing of transferrin decreased radiation-induced cell death. In addition, radiation increased lysosomal membrane permeabilization (LMP) and the release of lysosomal iron and cathepsins, while cathepsins silencing failed to change cell viability. Radiation-induced iron accumulation increased Reactive oxygen species (ROS) generation via the Fenton reaction and increased autophagy in a time-dependent manner. DFO, N-acetylcysteine (NAC), and overexpression of superoxide dismutase 2 (SOD2) decreased ROS generation, autophagy, and cell death. To summarize, for the first time, we found that radiation-induced autophagic cell death was iron-dependent in breast cancer MDA-MB-231 cells. These results provide new insights into the cell death process of cancers and might conduce to the development and application of novel therapeutic strategies for patients with apoptosis-resistant breast cancer.
AIM:To investigate the expression patterns of D-serine and N-methyl-D-aspartate (NMDA) receptor 1 in the temporal lobes of patients with intractable epilepsy. MATERIAL and METHODS:Cortical temporal lobe brain tissue samples were collected from 20 patients with intractable epilepsy and 6 patients with brain trauma. The expression patterns of D-serine and NMDA receptor 1 were detected by immunofluorescence staining and western blot analysis. RESULTS:A total of 20 patients (11 males, 9 females) were included in the present study. D-serine expression was significantly higher in the neurons and glial cells of patients with intractable epilepsy than in control individuals. The mean integrated optical density (IOD) value for the intractable epilepsy group (13.37 ± 1.88) was significantly higher than that for the control group (9.27 ± 0.62, p<0.05). The mean absorbance value of the NMDA receptor 1 protein strip obtained from intractable epileptic patients was 0.4175 ± 0.2321, which was significantly higher than the value of 0.2402 ± 0.1458 for the control group (p<0.05).CONCLUSION: D-serine and NMDA receptor 1 expressions increased significantly in patients with intractable epilepsy compared with control patients. Therefore, the D-serine signaling pathway may represent a potential neurochemical target for epilepsy treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.