THE ANTIPROLIFERATIVE AND APOPTOTIC EFFECTS OF ANNONA MURICATA EXTRACT ON PROSTATE CANCER CELLS

Abstract

Annona muricata (AM), a tropical evergreen tree, also known as graviola, guanabana or soursop, belongs to the custard apple trees family known as the Annonaceae. It has become known as a “cancer killer” due to its ability to reduce the proliferation of 12 different types of tumors, including breast, prostrate, lung, colon and pancreatic cancer cells. The major phytochemical compounds that have been identified in AM are cyclic hexapeptides and annonaceous acetogenins (AAGs). AAGs have been reported to have promising anticancer activities in multidrug resistant cancers (MDR). The structure of AAGs is composed of adjacent tetrahydrofuranic rings flanked by hydroxyl groups and tetrahydropyranic rings or epoxides. It has been demonstrated in previous studies that AAGs possibly inhibit the ubiquinone‐linked NADH oxidase that is constitutively over expressed in the mitochondrial membrane of cancer cells, but only transiently expressed in normal cells. The purpose of this study was to evaluate the antiproliferative and apoptotic effects of Annona muricata extract on prostate cancer cells (PC3). PC3 cells were treated with Annona muricata aqueous, methanol and ethyl acetate extracts (1–100 μg/mL). A cell viability assay utilizing 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) was performed to evaluate the antiproliferative effects. The results demonstrated that Annona muricata ethyl acetate extract (AMEAE) produces significant reduction in cell viability (IC50 10 μg/mL). Furthermore, Western Blot analyses to test Bcl‐2 and Bax were performed onPC3 cells exposed to AMEAE. The extract showed significant reduction in the expression of the antiapoptotic protein Bcl‐2 with no effect in the expression of the proapoptotic protein Bax. Caspase 3/7 activities were also tested to verify its participation. These results suggested that the AMEAE reduces cell proliferation and/or produce cell death in PC3 cells by the induction of apoptosis. Further studies will confirm the application of this plant constituents in cancer therapy.