Brusatol Protects HepG2 Cells against Oxygen-Glucose Deprivation-Induced Injury via Inhibiting Mitochondrial Reactive Oxygen Species-Induced Oxidative Stress

Abstract

Background: It has been reported that brusatol (BRU) reduces cellular reactive oxygen species (ROS) level under hypoxia; here the protective effect of BRU against oxygen-glucose deprivation/reoxygenation (OGD-R)-induced injury in HepG2 cells and against anoxia/reoxygenation (A/R)-induced injury in rat liver mitochondria was investigated. Materials and Methods: OGD-R-induced HepG2 cell viability loss was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and trypan blue staining. Mitochondrial ROS level in HepG2 cells was measured by MitoSOX staining. The cellular malondialdehyde and adenosine triphosphate level was measured by commercial kits. The mitochondrial membrane potential in HepG2 cells was measured by JC-1 staining. The protein level was detected by Western blotting. Rat liver mitochondria were separated by differential centrifugation. A/R-induced injury in isolated rat liver mitochondria was established by using a Clark oxygen electrode. The ROS generation in isolated mitochondria was evaluated using Amplex red/horseradish peroxidase. Results: BRU reduced mitochondrial ROS level and alleviated oxidative injury in HepG2 cells, thereby significantly inhibited OGD-R-induced cell death. During OGD-R, BRU improved mitochondrial function and inhibited the release of cytochrome c. Furthermore, BRU showed a clear protective effect against A/R-induced injury in isolated rat liver mitochondria. When isolated rat liver mitochondria were pretreated with BRU, A/R-induced ROS generation was significantly decreased, and mitochondrial respiratory dysfunction was ameliorated. Conclusions: BRU pretreatment attenuated OGD-R-induced injury in HepG2 cells and A/R-induced injury in isolated rat liver mitochondria by inhibiting mitochondrial ROS-induced oxidative stress.

Anti-tumor Properties of Picrasma quassioides Extracts in H-RasG12V Liver Cancer Are Mediated Through ROS-dependent Mitochondrial Dysfunction

“…In this study, we found that after PQ treatment of HepG2 G12V cells, changes of mitochondrial membrane permeability (MMP) and ATP synthesis were detected. In other studies, such as treatment of HepG2 cells with Brusatol, an increase in intracellular ROS has been reported, causing mitochondrial dysfunction, a reduction in ATP synthesis, and release of pro-apoptotic molecules to cause apoptosis (31). This is consistent with our findings, but whether PQ can affect other functions of HepG2 G12V cells was unknown.…”

NRF2 regulates the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via FOCAD-FAK signaling pathway

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Withaferin A Increases the Effectiveness of Immune Checkpoint Blocker for the Treatment of Non-Small Cell Lung Cancer

“…The literature shows that ROS can play either an immunostimulatory or an immunoinhibitory effect in the TME based on the type of cells from which it is produced and their specific location within the TME [ 47 , 48 ]. While ROS can induce ICD, increase tumor antigenicity, and reprogram tumor-associated macrophages, it also represents a major immunosuppressive mechanism when released by MDSCs or T-regs [ 49 , 50 , 51 , 52 , 53 ]. However, WFA was found to inhibit MDSCs production of ROS in a 4T1 mouse model suggesting that WFA plays a dual role in ROS signaling based on the cellular context [ 36 ].…”