Delphinidin 3-sambubioside, a Hibiscus anthocyanin, induces apoptosis in human leukemia cells through reactive oxygen species-mediated mitochondrial pathway.
Delphinidin 3-sambubioside (Dp3-Sam), a Hibiscus anthocyanin, was isolated from the dried calices of Hibiscus sabdariffa L. Dp3-Sam could induce a dose-dependent apoptosis in human leukemia cells (HL-60) as characterized by cell morphology, DNA fragmentation, activation of caspase-3, -8, and -9, and inactivation of poly(ADP)ribose polymerase (PARP). Molecular data showed that Dp3-Sam induced Bid truncation, mitochondrial membrane potential (DeltaPsi(m)) loss, and cytochrome c release from mitochondria to cytosol. Moreover, Dp3-Sam caused a time- and dose-dependent elevation of intracellular reactive oxygen species (ROS) level in HL-60 cells, and antioxidants such as N-acetyl-L-cysteine (NAC) and catalase could effectively block Dp3-Sam-induced ROS generation, caspase-3 activity, and DNA fragmentation. These data indicate that Dp3-Sam might induce apoptosis in HL-60 cells through a ROS-mediated mitochondrial dysfunction pathway. These findings enhance our understanding for anticancer function of Hibiscus anthocyanins in herbal medicine.
Hou
De-Xing
DX
Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-0065, Japan. hou@chem.agri.kagoshima-u.ac.jp
Tong
Xuhui
X
Terahara
Norihiko
N
Luo
Dong
D
Fujii
Makoto
M
D000872:Anthocyanins / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006027:Glycosides / Q000302:isolation & purification / Q000494:pharmacology*; D018922:HL-60 Cells; D031584:Hibiscus / Q000737:chemistry*; D006801:Humans; D007938:Leukemia / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000872:Anthocyanins; D006027:Glycosides; D017382:Reactive Oxygen Species; C505011:delphinidin 3-sambubioside; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases