ABSTRACT
Hepatocellular carcinoma is one of the most common causes of cancer-related deaths globally. Bioavailable, effective and safe therapeutic agents are urgently needed for cancer treatment. This study evaluated the metabolomics profiling, anti-proliferative and pro-apoptotic effects of strigol/albumin/chitosan nanoparticles (S/A/CNP) on HepG2 cell line. The diameter of S/A/CNP was (5⯱â¯0.01) nm. The IC50 was 180.4â¯nM and 47.6â¯nM for Strigol1 and S/A/CNP, respectively, after incubation for 24â¯h with HepG2 cells. By increasing the concentration of S/A/CNP, there was chromatin condensation, degranulation in the cytoplasm and shrinking in cell size indicating pro-apoptotic activity. Metabolomics profiling of the exposed cells by LC/MS/MS revealed that S/A/CNP up-regulated epigenetic intermediates (spermine and spermidine) and down-regulated energy production pathway and significantly decreased glutamine (Pâ¯<â¯0.001). These findings demonstrated that S/A/CNP has anti-proliferative, apoptotic effects and modulate energetic, and epigenetic metabolites in the hepatocellular carcinoma cell line (HepG2).
Subject(s)
Carcinoma, Hepatocellular/drug therapy , Lactones/pharmacology , Liver Neoplasms/drug therapy , Nanoparticles , Apoptosis/drug effects , Carcinoma, Hepatocellular/genetics , Cell Proliferation/drug effects , Cell Survival/drug effects , Chitosan/chemistry , Chromatography, Liquid , Down-Regulation/drug effects , Hep G2 Cells , Humans , Inhibitory Concentration 50 , Lactones/administration & dosage , Liver Neoplasms/genetics , Metabolomics , Particle Size , Serum Albumin, Human/chemistry , Tandem Mass Spectrometry , Up-Regulation/drug effectsABSTRACT
Reactive oxygen species play a significant role in the pathogenesis of retinopathy in diabetes patients. The current study aimed to assess the effect of ethyl acetate extract (EAE) from Balanites aegyptiaca (10, 25 or 50 mg/kg b.w.) in experimental diabetic rats. To achieve this aim, five groups of male rats were included: control, diabetic, and diabetic rats treated with 10, 25, and 50 µg/kg b.w. of EAE for eight weeks. Our results suggests a protective role of EAE against oxidative stress induced by streptozocine. EAE treatment produced a reduction in blood glucose levels, HbA1c, malondialdehyde and vascular endothelial growth factor (VEGF) in diabetic retina (p < 0.001), as well as an enhancement in antioxidant capacity against streptozocine-induced oxidative stress. Tumor necrosis factor alpha (TNF-α), interleukin (IL-1ß) and vascular endothelial growth factor (VEGF) were significantly reduced in diabetic rats treated with EAE, compared with untreated diabetic rats. Analysis of EAE by GC-MS indicated the presence of ß-sistosterol. Overall, EAE modulates oxidative stress induced by streptozocine and enhances antioxidant activity, which may provide additional endothelial protection in retina of diabetic rats. These results hold great promise in the management of diabetic complications.