Cytotoxicity and mechanism(s) of action of Hypoxis spp. (African potato) against HeLa, HT-29 and MCF-7 cancer cell lines

Hypoxis is one of the medicinal plants most frequently used by the indigenous people of South Africa. Although many species are used, most research has focused on Hypoxis hemerocallidea with very little or no scientific evidence on other species. The main aim of this study was to investigate and compare the cytotoxicity and mechanisms of action of three Hypoxis spp., namely H. hemerocallidea, Hypoxis stellipilis and Hypoxis sobolifera var sobolifera. Cytotoxicity was determined against HeLa, HT-29 and MCF-7 cancer cell lines and peripheral blood mononuclear cells (PBMCs). DNA cell cycle arrest in the G1, S or G2/M phase was determined using propidium iodide staining. H. sobolifera, which showed the best cytotoxicity against all three cancer cell lines, was used to investigate caspase-3 and/or -7 activation and DNA fragmentation using fluorescence labelled primary caspase antibodies and the TUNEL-based assay, respectively. DNA cell cycle arrest occurred in the late G1 and/or early S phase, which was confirmed by increased p21(Waf1/Cip1) activation; caspase-7 was mainly activated in the HeLa and HT-29 cancer cell lines and DNA fragmentation occurred in all three cancer cell lines. This study provides the first data to show that the cytotoxic mechanism of Hypoxis is exerted through the induction of cell cycle arrest and apoptosis.