Delphinidin induces necrosis in hepatocellular carcinoma cells in the presence of 3-methyladenine, an autophagy inhibitor.

The present study was performed to determine whether anthocyanins could trigger different modes of cell death in different cancers. It was found that whereas cyanidin-3-rutinoside and delphinidin could induce apoptosis in leukemia cells, they caused growth retardation in hepatocellular carcinoma cells (HCC), which was accompanied with a significant cellular vacuolization. The latter was likely caused by macroautophagy and was completely suppressed by 3-methyladenine, an inhibitor of class III phosphoinositide 3-kinase that is important for autophagy activation, and by bafilomycin A1, which blocks lysosomal degradation. Delphinidin induced significant lipidation of LC3, an indication of macroautophagy, which was also suppressed by 3-methyladenine. Macroautophagy was required for the survival of delphinidin-treated HCC cells as inhibition with 3-methyladenine led to massive necrosis without caspase activation. Thus, anthocyanins could induce different modes of cell death for different cancers. Furthermore, anthocyanins could be used in combination with a macroautophagy inhibitor for treating cancers such as HCC.