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 EGFR-regulated signaling cascades such as MAPK7 / PI3K-Akt / mTOR / STAT upon
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.
Results: The fraction of acetogenin decreased the viability of EGF induced PA-1 ovarian cancer
cells that indicating the EGF inhibitory effects of acetogenin. The docking studies specifically illustrated
that when the acetogenin binding with tyrosine kinase (TK) and regulatory unit (RU) which
subsequently resulted in a reduction in EGF induced the survival of PA-1 ovarian cancer cells.
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 (phosphor-acceptor site) of EGFR, essential for phosphorylation
of substrates in the TK domain and RU which promote downstream signaling.
Conclusion: Acetogenin isolated from AM effectively inhibited the survival of PA-1 ovarian cancer
cells through impaired EGF signaling.
Keywords: Annona Muricata, fractionation, acetogenin, EGF, EGFR, PA-1 cells, in silico.
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