ANTICANCER ACTIVITY OF ANNONA MURICATA EXTRACT ON TRIPLE NEGATIVE BREAST CANCER CELLS AND ISOLATION/CHARCTERIZATION OF ACTIVE COMPOUNDS

Abstract

Triple negative breast cancer (TNBC) cells are a subtype of breast cancer that lack of estrogen receptors (ERs), progesterone receptors (PRs) and human epidermal growth factor receptor 2 (HER2). This type of breast cancer has poor prognosis and accounts for 15–20% of newly diagnosed breast cancer (BC) cases. Annona muricata is a tropical plant and has been used as a folk medicine to treat several diseases such as malaria, inflammation, diabetes and recently it was known to have anticancer activity on various cancer types. However, the underlying molecular mechanisms remain to be explored. The purpose of this study was to investigate the anti‐proliferative activity and mechanism of action of Annona muricata ethyl acetate (AMEA) extract and one active fraction on BT‐20 TNBC cells.The AMEA showed significant decrease on BT‐20 cell viability as determined by the MTS assay. Furthermore, the AMEA was subjected to preparative thin layer chromatography (TLC) and eight fractions were obtained. From the 8 fractions only fraction 4 (F4) showed significant reduction in cell viability by the MTS assay. Immunoblotting analysis revealed that AMEA and F4 produced anti‐proliferative effect via inhibiting the EGFR phosphorylation and the phosphorylation of its downstream signaling proteins including AKT and MAPK. These effects were accompanied with down‐regulation of cyclin D1 production resulting in cell cycle arrest at G1/S phase. Furthermore, NF‐κB was measured due to its involvement in the progression of cancer that overexpress EGFR as reported in several studies. It was found that AMEA and F4 decreased significantly NF‐κB p65 protein expression in the nuclear fraction, therefore, inhibiting its activation and preventing the induction of cell survival. Our data indicated that neither AMEA nor F4 had significant effect on apoptosis biomarkers when tested on Bcl‐2, Bax, cytochrome c and caspase 3/7 activities. Taken together, these findings provide a scientific basis for the molecular mechanism of action of Annona muricata extract and its active fraction F4 in the treatment of TNBC. It has been demonstrated the anti‐proliferative effect via EGFR‐mediated signaling pathways which includes AKT/MAPK/NF‐κB pathways and cyclin D1 inhibition. Further studies are required to demonstrate the applications of this natural product in breast cancer therapy.Support or Funding InformationThis work was funded by MCPHS UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.