Breast cancer is the most prevalent cancer in Sudan, where this malignancy is frequently treated using plant-based traditional medicine, especially in the areas with minimal modem medical care. The aim of the present study was to test the in vitro anti-breast cancer activity of Sudanese plants and to elucidate the mechanisms of action of isolated active ingredients. Nine parts from five Sudanese plants (Kigelia africana: fruit and bark, Hygrophila auriculata: whole plant and leaves, Aerva javanica: whole plant, Indigofera astragalina: whole plant and fruit, and Boscia senegalensis: leaves and fruit) were selected on the basis of their traditional use for the treatment of breast cancer. The growth inhibitory properties of the methanol extract of the nine plant parts were examined in four breast carcinoma (MCF7, MDA-MB-231, MDA-MB- 468 and SK-BR-3), a pancreatic carcinoma (MIA-Pa-Ca2), a normal non- transformed fibroblast (MRCS), and a normal endothelial cell line (HUVECs), to assess their selectivity in breast carcinoma, and to test their effect in transformed compared with non-transformed cells; which resulted in five active extracts. The extracts of whole I. astragalina and its fruit (family: Papilionaceae) demonstrated the highest growth inhibitory activity in the breast carcinomas (GI50: 11.8-31.1 ug/rnl.). Phenols are more concentrated in the fruit compared to the whole plant extract, while flavonoids are higher in the whole plant extract. Both of the extracts reduced the growth of human adenocarcinoma cells (MDA-MB-468, 72 h) which was the most sensitive cell line to the extracts (22.2 and 22.6 ug/ml, for extracts 6 and 7, respectively); and they increased the preG 1 phase and caused S phase arrest in MDA-MB- 468 cells (72 h), whereas the fruit caused G2/M phase arrest. Both extracts strongly induced early apoptosis compared to late apoptosis and necrosis in MDA-MB-468 cells (24 h); all which agreed with the simultaneous cell cycle and apoptosis examination of each extract in MDA-MB-468 cells (24 h) which exposed early apoptotic populations emerging from each of the cell cycle phases, with the highest percentage from the non-cycling preG 1 phase. The dose-and time-dependency of the pro-apoptotic activities of I. astragalina whole extract were confirmed by the increase of cleaved poly ADP-ribose polymerase (PARP) intensity in MDA-MB-468 cells (24 h and 48 h).