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Artonin E Induces Apoptosis via Mitochondrial Dysregulation in SKOV-3 Ovarian Cancer Cells

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dc.contributor.authorMashitoh Abd Rahmanen_US
dc.contributor.authorFaiqah Ramlien_US
dc.contributor.authorHamed Karimianen_US
dc.contributor.authorFirouzeh Dehghanen_US
dc.contributor.authorNoraziah Nordinen_US
dc.contributor.authorHapipah Mohd Alien_US
dc.contributor.authorSyam Mohanen_US
dc.contributor.authorNajihah Mohd Hashimen_US
dc.date.accessioned2024-05-27T14:58:57Z
dc.date.available2024-05-27T14:58:57Z
dc.date.issued2016
dc.descriptionVolume:11 Issue :3en_US
dc.description.abstractArtonin 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.en_US
dc.identifier.doi10.1371/journal.pone.0151466
dc.identifier.epage23
dc.identifier.issn1932-6203
dc.identifier.issue3
dc.identifier.spage1
dc.identifier.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151466
dc.identifier.urihttps://oarep.usim.edu.my/handle/123456789/4019
dc.identifier.volume11
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofPlos Oneen_US
dc.titleArtonin E Induces Apoptosis via Mitochondrial Dysregulation in SKOV-3 Ovarian Cancer Cellsen_US
dc.typeArticleen_US
dspace.entity.typePublication

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