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. &...
| Main Authors: | , , , |
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| Format: | Journal article |
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Medknow Publications
2017
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| Summary: | <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> |
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