Annonacin exerts antitumor activity through induction of apoptosis and extracellular signal-regulated kinase inhibition
<p><strong>Background:</strong> Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Annonacin, a natural pure compound extracted from the seeds of <em>Annona muricata</em>, is a potential alternative therapeutic agent to treat EC. &...
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| Format: | Journal article |
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Medknow Publications
2017
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| _version_ | 1797080354614411264 |
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| author | Yap, C Subramaniam, K Khor, S Chung, I |
| author_facet | Yap, C Subramaniam, K Khor, S Chung, I |
| author_sort | Yap, C |
| collection | OXFORD |
| description | <p><strong>Background:</strong> Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Annonacin, a natural pure compound extracted from the seeds of <em>Annona muricata</em>, is a potential alternative therapeutic agent to treat EC. </p> <p><strong>Objective:</strong> To study the antitumor activity of annonacin and its mechanism of action in EC cells (ECCs). </p> <p><strong>Materials and Methods:</strong> Viability of ECCs treated with annonacin for 72 h was determined using methyl thiazolyl tetrazolium assay. The induction of cell cycle arrest and apoptotic cell death was evaluated using propidium iodide and annexin V-PE/7-AAD assay, respectively. DNA strand breaks were visualized using transferase dUTP nick end labeling assay, and the effects of annonacin on survival signaling were determined using western blotting. </p> <p><strong>Results:</strong> Annonacin exhibited antiproliferative effects on EC cell lines (ECC-1 and HEC-1A) and primary cells (EC6-ept and EC14-ept) with EC<sub>50</sub>values ranging from 4.62 to 4.92 μg/ml. EC cells were shown arrested at G2/M phase after treated with 4 μg/ml of annonacin for 72 h. This led to a significant increase in apoptotic cell death (65.7%) in these cells when compared to vehicle-treated cells (<em>P</em> < 0.005). We further showed that annonacin-mediated apoptotic cell death was associated with an increase in caspase-3 cleavage and DNA fragmentation. Cell apoptosis was accompanied with downregulation of extracellular signal-regulated kinase survival protein expression and induction of G2/M cell cycle arrest. </p> <p><strong>Conclusion: </strong>Annonacin may be a potential novel therapeutic agent for EC patients.</p> |
| first_indexed | 2024-03-07T00:58:48Z |
| format | Journal article |
| id | oxford-uuid:890377f3-1dc6-4a7e-8e1e-f9225007659a |
| institution | University of Oxford |
| last_indexed | 2024-03-07T00:58:48Z |
| publishDate | 2017 |
| publisher | Medknow Publications |
| record_format | dspace |
| spelling | oxford-uuid:890377f3-1dc6-4a7e-8e1e-f9225007659a2022-03-26T22:21:33ZAnnonacin exerts antitumor activity through induction of apoptosis and extracellular signal-regulated kinase inhibitionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:890377f3-1dc6-4a7e-8e1e-f9225007659aSymplectic Elements at OxfordMedknow Publications2017Yap, CSubramaniam, KKhor, SChung, I<p><strong>Background:</strong> Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Annonacin, a natural pure compound extracted from the seeds of <em>Annona muricata</em>, is a potential alternative therapeutic agent to treat EC. </p> <p><strong>Objective:</strong> To study the antitumor activity of annonacin and its mechanism of action in EC cells (ECCs). </p> <p><strong>Materials and Methods:</strong> Viability of ECCs treated with annonacin for 72 h was determined using methyl thiazolyl tetrazolium assay. The induction of cell cycle arrest and apoptotic cell death was evaluated using propidium iodide and annexin V-PE/7-AAD assay, respectively. DNA strand breaks were visualized using transferase dUTP nick end labeling assay, and the effects of annonacin on survival signaling were determined using western blotting. </p> <p><strong>Results:</strong> Annonacin exhibited antiproliferative effects on EC cell lines (ECC-1 and HEC-1A) and primary cells (EC6-ept and EC14-ept) with EC<sub>50</sub>values ranging from 4.62 to 4.92 μg/ml. EC cells were shown arrested at G2/M phase after treated with 4 μg/ml of annonacin for 72 h. This led to a significant increase in apoptotic cell death (65.7%) in these cells when compared to vehicle-treated cells (<em>P</em> < 0.005). We further showed that annonacin-mediated apoptotic cell death was associated with an increase in caspase-3 cleavage and DNA fragmentation. Cell apoptosis was accompanied with downregulation of extracellular signal-regulated kinase survival protein expression and induction of G2/M cell cycle arrest. </p> <p><strong>Conclusion: </strong>Annonacin may be a potential novel therapeutic agent for EC patients.</p> |
| spellingShingle | Yap, C Subramaniam, K Khor, S Chung, I Annonacin exerts antitumor activity through induction of apoptosis and extracellular signal-regulated kinase inhibition |
| title | Annonacin exerts antitumor activity through induction of apoptosis and extracellular signal-regulated kinase inhibition |
| title_full | Annonacin exerts antitumor activity through induction of apoptosis and extracellular signal-regulated kinase inhibition |
| title_fullStr | Annonacin exerts antitumor activity through induction of apoptosis and extracellular signal-regulated kinase inhibition |
| title_full_unstemmed | Annonacin exerts antitumor activity through induction of apoptosis and extracellular signal-regulated kinase inhibition |
| title_short | Annonacin exerts antitumor activity through induction of apoptosis and extracellular signal-regulated kinase inhibition |
| title_sort | annonacin exerts antitumor activity through induction of apoptosis and extracellular signal regulated kinase inhibition |
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