title: Delphinidin induces necrosis in hepatocellular carcinoma cells in the presence of 3-methyladenine, an autophagy inhibitor.
abstract: 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.
authors.affiliation: Department of Pathology and Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Rentian
authors.initials: R
authors.lastname: Feng
authors.forename: Shiow Y
authors.initials: SY
authors.lastname: Wang
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Shi
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Yin
mesh_terms: 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
chemical_list: D000872:Anthocyanins; C017185:delphinidin