Graviola (Annona muricata) is a tropical plant with many traditional ethnobotanic uses
and pharmacologic applications. A metabolomic study of both aqueous and DMSO extracts from
Annona muricata leaves recently allowed us to identify dozens of bioactive compounds. In the present
study, we use a proteomic approach to detect altered patterns in proteins on both conditioned media
and extracts of HT-1080 fibrosarcoma cells under treatment conditions, revealing new potential
bioactivities of Annona muricata extracts. Our results reveal the complete sets of deregulated proteins
after treatment with aqueous and DMSO extracts from Annona muricata leaves. Functional enrichment
analysis of proteomic data suggests deregulation of cell cycle and iron metabolism, which are
experimentally validated in vitro. Additional experimental data reveal that DMSO extracts protect
HT-1080 fibrosarcoma cells and HMEC-1 endothelial cells from ferroptosis. Data from our proteomic
study are available via ProteomeXchange with identifier PXD042354.