Artonin E Induces Apoptosis via Mitochondrial Dysregulation in SKOV-3 Ovarian Cancer Cells
| Autor: | Syam Mohan, Noraziah Nordin, Hamed Karimian, Mashitoh Abd Rahman, Firouzeh Dehghan, Hapipah Mohd Ali, Najihah Mohd Hashim, Faiqah Ramli |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell Membranes Cancer Treatment lcsh:Medicine Apoptosis DNA laddering Biochemistry chemistry.chemical_compound 0302 clinical medicine Medicine and Health Sciences Enzyme assays Cell Cycle and Cell Division Colorimetric assays lcsh:Science Bioassays and physiological analysis Energy-Producing Organelles Staining Ovarian Neoplasms Caspase 8 Multidisciplinary MTT assay Cell Death Molecular Structure Caspase 3 Cell Staining Cytochromes c Cell cycle Flow Cytometry Caspase 9 Mitochondria Ovarian Cancer Oncology Proto-Oncogene Proteins c-bcl-2 Cell Processes 030220 oncology & carcinogenesis S Phase Cell Cycle Checkpoints Female Cellular Structures and Organelles Research Article Programmed cell death Cell Survival Blotting Western DNA Fragmentation Biology Bioenergetics 03 medical and health sciences Inhibitory Concentration 50 Cell Line Tumor Survivin Humans Propidium iodide Cell Proliferation Flavonoids Cell growth lcsh:R Biology and Life Sciences Cancers and Neoplasms Cell Biology Molecular biology Research and analysis methods Enzyme Activation 030104 developmental biology chemistry Specimen Preparation and Treatment Biochemical analysis lcsh:Q Reactive Oxygen Species Gynecological Tumors Artocarpus |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 3, p e0151466 (2016) |
| ISSN: | 1932-6203 |
| Popis: | Artonin E is a prenylated flavonoid isolated from the stem bark of Artocarpus elasticus Reinw.(Moraceae). This study aimed to investigate the apoptotic mechanisms induced by artonin E in a metastatic human ovarian cancer cell line SKOV-3 in vitro. MTT assay, clonogenic assay, acridine orange and propidium iodide double staining, cell cycle and annexin V analyses were performed to explore the mode of artonin E-induced cell death at different time points. DNA laddering, activation of caspases-3, -8, and -9, multi-parametric cytotoxicity-3 analysis by high-content screening, measurement of reactive oxygen species generation, and Western blot were employed to study the pathways involved in the apoptosis. MTT results showed that artonin E inhibited the growth of SKOV-3 cells, with IC50 values of 6.5±0.5 μg/mL after 72 h treatment, and showed less toxicity toward a normal human ovarian cell line T1074, with IC50 value of 32.5±0.5 μg/mL. Results showed that artonin E induced apoptosis and cell cycle arrest at the S phase. This compound also promoted the activation of caspases-3, -8, and -9. Further investigation into the depletion of mitochondrial membrane potential and release of cytochrome c revealed that artonin E treatment induced apoptosis via regulation of the expression of pro-survival and pro-apoptotic Bcl-2 family members. The expression levels of survivin and HSP70 proteins were also down regulated in SKOV-3 cells treated with artonin E. We propose that artonin E induced an antiproliferative effect that led to S phase cell cycle arrest and apoptosis through dysregulation of mitochondrial pathways, particularly the pro- and anti-apoptosis signaling pathways. |
| Databáze: | OpenAIRE |
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