Diferuloylputrescine, a predominant phenolic amide in corn bran, potently induces apoptosis in human leukemia U937 cells

The purpose of this study was to investigate how proliferation and apoptosis in human leukemia U937 cells are affected by four hydroxycinnamic acid derivatives (HCADs) in corn (Zea mays L.) bran: p-coumaric (CA), ferulic acids (FA), dicoumaroylputrescine (DCP), and diferuloylputrescine (DFP). Of the four HCADs, DFP dose dependently exerted the strongest cytotoxic effect and induction of apoptosis in the U937 cells. In addition, DFP induced distinct morphological changes characteristic of cellular apoptosis, such as chromatin condensation, apoptotic bodies, and DNA fragmentations. The DFP-induced apoptosis was also associated with released cytochrome c in the cytosol with activation of caspase 3, together with the downregulation of anti-apoptotic proteins, including XIAP and cIAP2, Bcl-2, and Mcl-1. Finally, the DFP-induced apoptosis was a cell-specific response in leukemia cells, as compared with those of other cancer cells, such as Caki, HT29, SK-Hep1, and MDA-MB231. Thus, these results suggest that DFP may be useful as a potential source of natural antileukemic agents.