In the healthcare sector, phytocompounds are known to be beneficial by contributing or alleviating a variety of diseases. Studies have demonstrated the progressive effects of phytocompounds on immune-related diseases and to exhibit anticancer effects. Graviola tree is an evergreen tree with its extracts (leafs and seeds) been reported having anticancer properties, but the precise target of action is not clear. Using an in silico approach, we predicted that
annonacin, an Acetogenin, the active agent found in Graviola leaf extract (GLE) to potentially act as a novel inhibitor of both
sodium/
potassium (NKA) and sarcoplasmic reticulum (SERCA)
ATPase pumps. We were able to validate and confirm the in silico studies by showing that GLE inhibited NKA and SERCA activity in intact cells. In the present study, we also demonstrated the antiproliferative and anticancer effects of GLE in a variety of
cancer cell lines with limited toxic effects on non-transformed cells. Moreover, our results revealed that known inhibitors of both NKA and SERCA pumps could also promote cell death in several
cancer cell lines. In addition, a mouse xenograft
cancer model showed GLE as able to reduce
tumor size and progression. Finally, bioprofiling studies indicated a strong correlation between overexpression of both NKA and SERCA gene expression vs. survival rates. Overall, our results demonstrated that GLE can promote selective
cancer cell death via inhibiting NKA and SERCA, and thus can be considered as a potential novel treatment for
cancer. After molecular analysis of GLE by liquid chromatography-mass spectrometry and ESI-QTOF-MS analysis, it was found that the MS spectrum of the high abundant chromatographic peak purified sample highly consisted of
annonacin.