Pro-apoptotic activity against cancer stem cells differs between different parts of sweet sorghum

• Sweet sorghum (SS) is a rich source of bioactive 3-deoxyanthocyanidins.
• Dermal and seed head (SH) phenolics were most potent apoptotic agents.
• Dermal and SH induced apoptosis were p53-dependent and partially p53-dependent, respectively.
• SS bioactives targeted Wnt/β-catenin signalling pathway proteins.

The extracts from sweet sorghum stalk were previously shown to eliminate human colon cancer stem cells (CCSC) in a partial p53-dependent fashion. However, the underlying mechanisms remain unknown. In this study, we transfected CCSC with shRNA against p53 and treated with sweet sorghum phenolics extracted from different plant components. While all sweet sorghum components demonstrated anti-proliferative and pro-apoptotic effects in CCSC, phenolics extracted from the dermal layer and seed head were more potent in eliminating CCSC by elevating caspase 3/7 activity, poly ADP-ribose polymerase cleavage, and DNA fragmentation in a p53-dependent and partial p53-dependent manner, respectively. These effects were associated with decreases in β-catenin, cyclin D1, cMyc, and survivin protein levels. These results suggest that the anti-proliferative and pro-apoptotic effects of sweet sorghum extracts against CCSC are potentially via suppression of Wnt/β-catenin signalling in a p53-dependent (dermal layer) and partial p53-dependent (seed head) manner.