Artonin E Induces Apoptosis via Mitochondrial Dysregulation in SKOV-3 Ovarian Cancer CellsReport as inadecuate




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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-3analysis 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±0.5μg-mL after 72 h treatment, and showed less toxicity toward a normal human ovarian cell lineT1074, with IC50 value of 32.5±0.5μg-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.



Author: Mashitoh Abd Rahman , Faiqah Ramli , Hamed Karimian, Firouzeh Dehghan, Noraziah Nordin, Hapipah Mohd Ali, Syam Mohan, Najihah Moh

Source: http://plos.srce.hr/



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