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.
SUMMARY: We aimed to study the antitumor activity of annonacin and its mechanism of action in endometrial cancer cells. Annonacin exerted antiproliferation effects on both endometrial cancer cell lines and primary cells via induction of apoptosis and inhibition of extracellular signal-regulated kinase. Our data represented that annonacin could be an alternative therapeutic treatment to combat endometrial cancer. 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.
Background: Porcupine dates are phytobezoar stones that are used in Traditional Chinese Medicine (TCM) treatments against cancer, postsurgical recovery, dengue fever, etc. The medicinal values have not been scientifically investigated due to the availability and high pricing of the dates.
Objectives: This paper represents the first report on the phytochemical content, in vitro antioxidant and intracellular reactive oxygen species (ROS)/reactive nitrogen species (RNS) scavenging properties of the extracts of three porcupine dates: grassy date (GD), black date (BD), and powdery date (PD).
Materials and Methods: Dried samples were extracted with methanol and lyophilized. Samples were screened for phytochemical constituents, in vitro antioxidant assays based on total phenolic content (TPC), free radical scavenging, and ferric reducing power (FRP) as well as intracellular ROS and RNS scavenging properties.
Results: Phytochemical screening and total tannins assay revealed that tannins, cardiac glycosides, and terpenoids were found in all porcupine dates with tannins forming the major portion of the TPC. In comparison to GD, BD and PD were found to contain significantly high TPC, radical scavenging activity, and FRP. At 200 μg/ml, BD and PD remarkably scavenged 2, 2-azobis (2-amidinopropane) dihydrochloride-induced ROS in RAW264.7 cells and significantly reduced nitric oxide in lipopolysaccharide-stimulated cells.
Conclusion: Overall, BD and PD exhibited promising in vitro antioxidant as well as intracellular ROS/RNS scavenging properties.
SUMMARY: Tannins, cardiac glycoside, and terpenoids were found in all three types of porcupine dates with tannins being the major compoundsAntioxidant contents and properties of three dates were in the order black date (BD) > powdery date (PD) > grassy dateBD and PD extracts showed significant intracellular reactive oxygen species and reactive nitrogen species scavenging properties. Abbreviations Used: TCM: Traditional Chinese Medicine, BD: Black date, GD: Grassy date, PD: Powdery date, TPC: Total phenolic content, FRS: Free radical scavenging, FRP: Ferric reducing power, NO: Nitric oxide, ROS: Reactive oxygen species, RNS: Reactive nitrogen species, GAE: Gallic acid equivalent, AAE: Ascorbic acid equivalent, PVPP: Polyvinylpolypyrrolidone, DCFH-DA: Dichloro-dihydro-fluorescein diacetate, AAPH: 2, 2-azobis (2-amidinopropane) dihydrochloride, LPS: Lipopolysaccharide.