ABSTRACT
Acute myeloid leukemia (AML) is an aggressive haematological malignancy characterized by highly proliferative accumulation of immature and dysfunctional myeloid cells. Quercetin (Qu), one kind of flavonoid, exhibits anti-cancer property in multiple types of solid tumor, but its effect on acute myeloid leukemia is less studied, and the underlying mechanisms still largely unknown. This study aimed to explore the specific target and potential mechanism of quercetin-induced cell death in AML. First, we found that quercetin induces cell death in the form of apoptosis, which was caspase dependent. Second, we found that quercetin-induced apoptosis depends on the decrease of mitochondria membrane potential (MMP) and Bcl-2 proteins. With quantitative chemical proteomics, we observed the downregulation of VEGFR2 and PI3K/Akt signaling in quercetin-treated cells. Consistently, cell studies also identified that VEGFR2 and PI3K/Akt signaling pathways are involved in the action of quercetin on mitochondria and Bcl-2 proteins. The decrease of MMP and cell death could be rescued when PI3K/Akt signaling is activated, suggesting that VEGFR2 and PI3K/Akt exert as upstream regulators for quercetin effect on apoptosis induction in AML cells. In conclusion, our findings from this study provide convincing evidence that quercetin induces cell death via downregulation of VEGF/Akt signaling pathways and mitochondria-mediated apoptosis in AML cells.
ABSTRACT
[This corrects the article DOI: 10.3389/fphar.2020.534171.].
ABSTRACT
Caveolin-3 (CAV3) is a muscle specific protein that plays an important role in maintaining muscle health and glucose homeostasis in vivo. A novel autosomal dominant form of LGMD-1C in humans is due to a P104L mutation within the coding sequence of the human CAV3 gene. The mechanism by which the LGMD-1C mutation leads to muscle weakness remains unknown. Our objective was to determine whether muscle weakness was related to the imbalance of glucose metabolism. We found that when the P104L mutation was transiently transfected into C2C12 cells, there was decreased glucose uptake and glycogen synthesis after insulin stimulation. Immunoblotting analysis showed that the P104L mutation resulted in decreased expression of CAV3, CAV1 and pAkt. Confocal immunomicroscopy indicated that the P104L mutation reduced CAV3 and GLUT4 in the cell membrane, which accumulated mainly near the nucleus. This work is the first report of an association between muscle weakness due to LGMD-1C and energy metabolism. The P104L mutation led to a decrease in C2C12 muscle glucose uptake and glycogen synthesis and may be involved in the pathogenesis of LGMD-1C.
Subject(s)
Caveolin 3/genetics , Glucose Transporter Type 4/genetics , Glucose/metabolism , Muscle Cells/metabolism , Mutation , Amino Acid Sequence , Animals , Caveolin 1/genetics , Caveolin 1/metabolism , Caveolin 3/metabolism , Cell Differentiation/drug effects , Cell Line , Cell Membrane/metabolism , Cell Membrane/ultrastructure , Gene Expression Regulation , Genes, Reporter , Glucose Transporter Type 4/metabolism , Glycogen/biosynthesis , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Humans , Insulin/pharmacology , Mice , Muscle Cells/cytology , Muscle Cells/drug effects , Muscular Dystrophies, Limb-Girdle/genetics , Muscular Dystrophies, Limb-Girdle/pathology , Myoblasts/cytology , Myoblasts/metabolism , Protein Structure, Secondary , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , TransgenesABSTRACT
Cationic liposome is a greatly promising gene carrier. In this paper, the structure trait of cationic liposome was briefly introduced, the mechanism of cationic liposomes mediated gene delivery and the main influencing factor of transfection efficiency in the transfection process were discussed chiefly.
