Pharmacognosy Research

ORIGINAL ARTICLE
Year
: 2017  |  Volume : 9  |  Issue : 4  |  Page : 378--383

Annonacin exerts antitumor activity through induction of apoptosis and extracellular signal-regulated kinase inhibition


Chee Voon Yap, Kavita S Subramaniam, Sik Wey Khor, Ivy Chung 
 Department of Pharmacology, Faculty of Medicine, University of Malaya; Department of Pharmacology, UM Cancer Research Institute, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur 50603, Malaysia

Correspondence Address:
Ivy Chung
Department of Pharmacology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur
Malaysia

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 EC50values 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 (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. Abbreviations Used: 7-AAD: 7-Amino-Actinomycin, ATP: Adenosine diphosphate, BSA: Bovine serum albumin, DNA: Deoxyribonucleic acid, EC: Endometrial cancer, ECC-1: Endometrial cancer cell-1, EC50: Half maximal effective concentration, Ept: Epithelial, FBS: Fetal bovine serum, HEC-1A: Human endometrial carcinoma-1A, MTT: Methyl thiazolyl tetrazolium, NaCl: Sodium chloride, NADH: Nicotinamide adenine dinucleotide, RPMI 1640: Roswell Park Memorial Institute Medium, SDS: Sodium dodecyl sulfate


How to cite this article:
Yap CV, Subramaniam KS, Khor SW, Chung I. Annonacin exerts antitumor activity through induction of apoptosis and extracellular signal-regulated kinase inhibition.Phcog Res 2017;9:378-383


How to cite this URL:
Yap CV, Subramaniam KS, Khor SW, Chung I. Annonacin exerts antitumor activity through induction of apoptosis and extracellular signal-regulated kinase inhibition. Phcog Res [serial online] 2017 [cited 2020 Sep 28 ];9:378-383
Available from: http://www.phcogres.com/article.asp?issn=0974-8490;year=2017;volume=9;issue=4;spage=378;epage=383;aulast=Yap;type=0