cytochrome-c-t and vexibinol

A compound isolated from Sophora flavescens-sophoraflavanone G (SG)-showed anti-tumor and anti-inflammatory properties. We previously demonstrated that SG promoted apoptosis in human leukemia HL-60 cells. In the present study, we investigated the effects of SG on apoptosis in human breast cancer MDA-MB-231 cells, and explored the underlying molecular mechanisms.. MDA-MB-231 cells were treated with various SG concentrations, and cell viability was evaluated by MTT assay. Apoptotic signal proteins were detected by western blotting, and cell apoptosis was assessed using flow cytometry.. Our results demonstrated that SG induced nuclear condensation, DNA fragmentation, reactive oxygen species production, and increased cell apoptosis in MDA-MB-231 cells. SG also suppressed migration and invasion, likely via blockage of the MAPK pathway. In the apoptotic signaling pathway, SG increased cleaved caspase-8, caspase-3, and caspase-9. SG treatment also decreased Bcl-2 and Bcl-xL expression, increased Bax expression, and prompted release of more cytochrome c from mitochondria to the cytoplasm in MDA-MB-231 cells.. Overall, our findings suggest that SG might increase apoptosis, and decrease migration and invasion, in MDA-MB-231 cells through suppression of a MAPK-related pathway.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Autophagy; Caspases; Cell Line, Tumor; Cell Movement; Cell Survival; Cytochromes c; Female; Flavanones; Humans; MAP Kinase Signaling System; Mitochondria; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Sophora; Triple Negative Breast Neoplasms

Sophoraflavanone G (SG) was isolated from Sophora flavescens. Previously, we have found that SG is able to suppress the inflammatory response in lipopolysaccharide-stimulated RAW 264.7 macrophages. This study aimed to evaluate the effects of SG on apoptosis, and explore its molecular mechanism in human leukemia HL-60 cells. HL-60 cells were treated with various concentrations of SG (3-30 [Formula: see text]M). The viability of the HL-60 cells was assessed using the MTT method, and the nuclear condensation indicative of apoptosis was observed by DAPI fluorescence staining. In addition, apoptotic signal proteins were examined using Western blotting. The results showed that apoptosis, including DNA fragmentation and nuclear condensation, increased significantly in SG-treated HL-60 cells. SG activated caspase-3 and caspase-9, and downregulated Bcl-2 and Bcl-xL. SG also upregulated Bax and released cytochrome c from the mitochondria into the cytoplasm, enabling apoptosis via the mitochondrially-mediated "intrinsic" pathway. Additionally, SG was able to cleave poly (ADP-ribose) polymerase 1 and activate mitogen-activated protein kinase (MAPK) pathways. These results suggest that SG might increase the effect of apoptosis on HL-60 cells through caspase-3 activation, mitochondrial-mediated pathways, and the MAPK pathway.

Topics: Anti-Inflammatory Agents; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Caspase 3; Caspase 9; Cytochromes c; DNA Fragmentation; Dose-Response Relationship, Drug; Down-Regulation; Flavanones; HL-60 Cells; Humans; Leukemia, Promyelocytic, Acute; Mitochondria; Mitogen-Activated Protein Kinases; Poly (ADP-Ribose) Polymerase-1; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Sophora; Up-Regulation