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

Yap, C; Subramaniam, K; Khor, S; Chung, I

Women's Health Collection

Journal article

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

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 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.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Yap, C., Subramaniam, K., Khor, S., & Chung, I. (2017). Annonacin exerts antitumor activity through induction of apoptosis and extracellular signal-regulated kinase inhibition. Pharmacognosy Research, 9(4), 378–383.

MLA Style

Yap, C, et al. “Annonacin Exerts Antitumor Activity through Induction of Apoptosis and Extracellular Signal-Regulated Kinase Inhibition.” Pharmacognosy Research, vol. 9, no. 4, 2017, pp. 378–83.

Chicago Style

Yap, C, K Subramaniam, S Khor, and I Chung. 2017. “Annonacin Exerts Antitumor Activity through Induction of Apoptosis and Extracellular Signal-Regulated Kinase Inhibition.” Pharmacognosy Research 9 (4): 378–83.
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