Background:
In individuals with ovarian cancer, an increase in the circulating level of the epidermal growth
factor (EGF) is readily apparent. Ovarian cancer cells exhibit signaling pathway of the epidermal growth factor (EGFR) and
respond to the EGF. Annona Muricata (AM) has been shown to decrease ovarian cell proliferation however, role of AM in
regulating EGF actions is not yet to be reported.
Objective:
In this study, we proposed that the fractionated compound acetogenin can inhibit the activation of EGFRregulated signaling cascades such as MAPK7 / PI3K-Akt / mTOR / STAT upon EGF stimulation.
Methods:
Ethanolic extract was prepared for the whole AM plant and Thin Layer Chromatography (TLC) was performed to
characterize the secondary metabolites and each fraction was assessed using kedde reagent for the presence of acetogenin.
The effects of acetogenins were then tested on the survival of PA-1 ovarian cancer cells under basal and EGF stimulated
conditions. To delineate the role of acetogenin in EGFR signaling cascades, the in silico docking studies were conducted.
Discussion:
The vital regulatory role of acetogenin reported in this study indicate significant anticancer activities of
acetogenin from AM. The in silico study of the acetogenin function predicted that it binds specifically to Asp837 (phosphoracceptor site) of EGFR, essential for phosphorylation of substrates in the TK domain and RU which promote downstream
signaling.
Conclusion:
This study, proposed that acetogenin isolated from AM effectively inhibited the survival of PA-1 ovarian
cancer cells through impaired EGF signaling.