Publication:
Liriodenine, An Aporphine Alkaloid From Enicosanthellum Pulchrum, Inhibits Proliferation Of Human Ovarian Cancer Cells Through Induction Of Apoptosis Via The Mitochondrial Signaling Pathway And Blocking Cell Cycle Progression

cris.lastimport.scopus2025-11-14T15:47:53Z
cris.lastimport.wos2025-11-14T15:47:34Z
dc.contributor.authorNoraziah Nordinen_US
dc.contributor.authorNazia Abdul Majiden_US
dc.contributor.authorNajihah Mohd Hashimen_US
dc.contributor.authorMashitoh Abd Rahmanen_US
dc.contributor.authorZalila Hassanen_US
dc.contributor.authorHapipah Mohd Alien_US
dc.date.accessioned2024-05-28T04:30:09Z
dc.date.available2024-05-28T04:30:09Z
dc.date.issued2015
dc.descriptionVolume :9 (Page: 1437-1448)en_US
dc.description.abstractEnicosanthellum pulchrum is a tropical plant from Malaysia and belongs to the Annonaceae family. This plant is rich in isoquinoline alkaloids. In the present study, liriodenine, an isoquinoline alkaloid, was examined as a potential anticancer agent, particularly in ovarian cancer. Liriodenine was isolated by preparative high-performance liquid chromatography. Cell viability was performed to determine the cytotoxicity, whilst the detection of morphological changes was carried out by acridine orange/propidium iodide assay. Initial and late apoptosis was examined by Annexin V-fluorescein isothiocyanate and DNA laddering assays, respectively. The involvement of pathways was detected via caspase-3, caspase-8, and caspase-9 analyses. Confirmation of pathways was further performed in mitochondria using a cytotoxicity 3 assay. Apoptosis was confirmed at the protein level, including Bax, Bcl-2, and survivin, while interruption of the cell cycle was used for final validation of apoptosis. The result showed that liriodenine inhibits proliferation of CAOV-3 cells at 37.3 µM after 24 hours of exposure. Changes in cell morphology were detected by the presence of cell membrane blebbing, chromatin condensation, and formation of apoptotic bodies. Early apoptosis was observed by Annexin V-fluorescein isothiocyanate bound to the cell membrane as early as 24 hours. Liriodenine activated the intrinsic pathway by induction of caspase-3 and caspase-9. Involvement of the intrinsic pathway in the mitochondria could be seen, with a significant increase in mitochondrial permeability and cytochrome c release, whereas the mitochondrial membrane potential was decreased. DNA fragmentation occurred at 72 hours upon exposure to liriodenine. The presence of DNA fragmentation indicates the CAOV-3 cells undergo late apoptosis or final stage of apoptosis. Confirmation of apoptosis at the protein level showed overexpression of Bax and suppression of Bcl-2 and survivin. Liriodenine inhibits progression of the CAOV-3 cell cycle in S phase. These findings indicate that liriodenine could be considered as a promising anticancer agent.en_US
dc.identifier.citationNordin N, Abdul Majid N, Mohd Hashim N, Abd Rahman M, Hassan Z, Mohd Ali H. Liriodenine, an aporphine alkaloid from ­Enico­santhellum pulchrum, inhibits proliferation of human ovarian cancer cells through induction of apoptosis via the mitochondrial signaling pathway and blocking cell cycle progression. Drug Des Devel Ther. 2015;9:1437-1448en_US
dc.identifier.doi10.2147/DDDT.S77727
dc.identifier.epage1448
dc.identifier.issn1177-8881
dc.identifier.spage1437
dc.identifier.urihttps://www.dovepress.com/liriodenine-an-aporphine-alkaloid-from-shyenicoshysanthellum-pulchrum--peer-reviewed-fulltext-article-DDDT
dc.identifier.urihttps://oarep.usim.edu.my/handle/123456789/5770
dc.identifier.volume9
dc.language.isoen_USen_US
dc.publisherDovepressen_US
dc.relation.ispartofDrug Design, Development and Therapyen_US
dc.subjectEnicosanthellum pulchrum, liriodenine, ovarian cancer, CAOV-3, apoptosisen_US
dc.titleLiriodenine, An Aporphine Alkaloid From Enicosanthellum Pulchrum, Inhibits Proliferation Of Human Ovarian Cancer Cells Through Induction Of Apoptosis Via The Mitochondrial Signaling Pathway And Blocking Cell Cycle Progressionen_US
dc.typeArticleen_US
dspace.entity.typePublication

Files

Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Liriodenine, an aporphine alkaloid from Enicosanthellum pulchrum, inhibits proliferation of human ovarian cancer cells through induction of apoptosis via the mitochondrial signaling pathway and blocking cell cycle progression.pdf
Size:
2.94 MB
Format:
Adobe Portable Document Format