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Liriodenine, an aporphine alkaloid from ­Enico­santhellum pulchrum, inhibits proliferation of human ovarian cancer cells through induction of apoptosis via the mitochondrial signaling pathway and…

Overview of attention for article published in Drug Design, Development and Therapy, March 2015
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Title
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
Published in
Drug Design, Development and Therapy, March 2015
DOI 10.2147/dddt.s77727
Pubmed ID
Authors

Nazia Majd, Noraziah Nordin, Najihah Mohd Hashim, Mashitoh Abd Rahman, Zalila Hassan, Hapipah Mohd Ali

Abstract

Enicosanthellum 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.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 5 17%
Student > Doctoral Student 3 10%
Lecturer 3 10%
Student > Ph. D. Student 3 10%
Student > Master 3 10%
Other 7 24%
Unknown 5 17%
Readers by discipline Count As %
Medicine and Dentistry 7 24%
Chemistry 5 17%
Biochemistry, Genetics and Molecular Biology 4 14%
Pharmacology, Toxicology and Pharmaceutical Science 3 10%
Agricultural and Biological Sciences 1 3%
Other 4 14%
Unknown 5 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 March 2015.
All research outputs
#4,096,635
of 4,897,794 outputs
Outputs from Drug Design, Development and Therapy
#493
of 715 outputs
Outputs of similar age
#121,300
of 145,296 outputs
Outputs of similar age from Drug Design, Development and Therapy
#7
of 7 outputs
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So far Altmetric has tracked 715 research outputs from this source. They receive a mean Attention Score of 2.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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