Acetogenin Extracted from Annona muricata Prevented the Actions of EGF in PA-1 Ovarian Cancer Cells.

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 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. 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.

Safety assessment of ethanolic root extract of Zaleya decandra (EEZD) in Wistar rats.

Zaleya decandra is a prostrate, glabrous, succulent herb of the family Aizoaceae. In recent years the pharmacological efficacy of the plant such as the hepatoprotective, antimicrobial, antidiabetic, anti-inflammatory and anticancer activities has been reported. However, a long-term toxicity study of Z. decandra is yet to be carried out. In the present study, the acute dose of 2000 mg/kg b.w. of ethanolic extract of Z. decandra (EEZD) administered orally to Wistar rats gained gradual weight with time and appeared healthy without any record of mortality. In the sub-chronic toxicity study, the rats showed no remarkable increase or decrease in their weight even at the highest dose of 500 mg/kg b.w. The haematological, biochemistry and serum marker enzyme parameters did not show any dose dependent change in the values. Further, the histology micrographs confirmed that the tissue architecture of all the vital organs were not affected by EEZD treatment. Hence, the EEZD (500 mg/kg b.w.) is considered safe for a 90-day period. Therefore, the present study warrants extensive investigation of EEZD using higher pre-clinical model system to substantiate the findings. The GC-MS analysis revealed the presence of 39 phytoconstituents including octadecenoic acid, hexadecanoic and phytosterols such as campesterol, sitosterol and stigmasterol.