Molecular investigation of the effect of Annona muricata plant extract on the breast cancer cell line and Drosophila melanogaster model organism

Cancer, including breast cancer, has become a major health problem worldwide. Although there are great advances in chemotherapy and radiotherapy methods used in cancer treatment, most cancer patients use alternative medicine methods which are out of the scope of modern medical treatment due to their limitations and obvious side effects. Within the scope of alternative medicine, Annona muricata, that is widely available in tropical regions around the world, contains compounds that are effective against cancer. This study was carried out to investigate the anticancer biological activity of Annona muricata plant known as the cinnamon apple in our country. As a result of toxicity analysis, IC50 value; in two-dimensional MCF-7 cells was 290 μg.mℓ-1, in two-dimensional MDA-MB-231 cells was 330 μg.mℓ-1, in three-dimensional MCF-7 and MDA-MB-231 cells were 0.005 g.mℓ-1, and in Drosophila melanogaster model organism was determined as 0.118 g.mℓ-1. After application, in the MDA-MB-231 and MCF-7 cell lines, expression levels of Bcl-2, Bad, AKT1, and H-prune genes; in Drosophila melanogaster; expression levels of Pn, Buffy, CG15530 and Akt1 genes were determined by reverse transcription polymerase chain reaction. In gene expression analysis was observed that the expression of H-prune and AKT1 genes decreased and Drosophila melanogaster CG15530 proapoptotic gene expression increased. In the last stage of the study; isoquercetin, roseoside, coreximine, anonaine, and arianacin acetogenins which are present in Annona muricata, the binding energy level with human Bcl-2, Bad and AKT1 proteins was calculated by molecular docking method. Compared with abemaciclib, which is used as a preclinical drug, has been observed that the isoquercetin molecule has high affinity with Bcl-2, Bad and AKT1 proteins. As a result of the analysis in vivo, in vitro and bioinformatics; Annona muricata plant extract has been observed to be effective against breast cancer and likely to be a potential drug.