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.
Feng
Rentian
R
Department of Pathology and Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Wang
Shiow Y
SY
Shi
Ying-Hong
YH
Fan
Jia
J
Yin
Xiao-Ming
XM
D000872:Anthocyanins / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D009336:Necrosis
D000872:Anthocyanins; C017185:delphinidin