@article {456, title = {Annonacin Exerts Antitumor Activity through Induction of Apoptosis and Extracellular Signal-regulated Kinase Inhibition}, journal = {Pharmacognosy Research}, volume = {9}, year = {2017}, month = {November 2017}, pages = {378-383}, type = {Original Article}, chapter = {378}, abstract = {

Background: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Annonacin, a natural pure compound extracted from the seeds of Annona muricata, is a potential alternative therapeutic agent to treat EC. Objective: To study the antitumor activity of annonacin and its mechanism of action in EC cells (ECCs). Materials and Methods: 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. Results: Annonacin exhibited antiproliferative effects on EC cell lines (ECC-1 and HEC-1A) and primary cells (EC6-ept and EC14-ept) with EC50 values ranging from 4.62 to 4.92 {\textmu}g/ml. EC cells were shown arrested at G2/M phase after treated with 4 {\textmu}g/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 (P \< 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. Conclusion: Annonacin may be a potential novel therapeutic agent for EC patients.

}, keywords = {Annona muricata, Apoptosis, caspase-3, Cell cycle arrest, Extracellular signal-regulated kinase, Uterine cancer}, doi = {10.4103/pr.pr_19_17}, author = {Chee Voon Yap and Kavita S Subramaniam and Sik Wey Khor and Ivy Chung} }