title: Polyphenols isolated from Allium cepa L. induces apoptosis by suppressing IAP-1 through inhibiting PI3K/Akt signaling pathways in human leukemic cells.
abstract: Allium cepa Linn is commonly used as supplementary folk remedy for cancer therapy. Evidence suggests that Allium extracts have anti-cancer properties. However, the mechanisms of the anti-cancer activity of A. cepa Linn are not fully elucidated in human cancer cells. In this study, we investigated anti-cancer effects of polyphenols extracted from lyophilized A. cepa Linn (PEAL) in human leukemia cells and their mechanisms. PEAL inhibited cancer cell growth by inducing caspase-dependent apoptosis. The apoptosis was suppressed by caspase 8 and 9 inhibitors. PEAL also up-regulated TNF-related apoptosis-inducing ligand (TRAIL) receptor DR5 and down-regulated survivin and cellular inhibitor of apoptosis 1 (cIAP-1). We confirmed these findings in other leukemic cells (THP-1, K562 cells). In addition, PEAL suppressed Akt activity and the PEAL-induced apoptosis was significantly attenuated in Akt-overexpressing U937 cells. In conclusion, our data suggested that PEAL induced caspase-dependent apoptosis in several human leukemic cells including U937 cells. The apoptosis was triggered through extrinsic pathway by up-regulating DR5 modulating as well as through intrinsic pathway by modulating IAP family members. In addition, PEAL induces caspase-dependent apoptosis at least in part through the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. This study provides evidence that PEAL might be useful for the treatment of leukemia.
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine and 3Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University, Busan 614-052, South Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Han
authors.forename: Won Sup
authors.initials: WS
authors.lastname: Lee
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Jung
authors.forename: Jae-Hun
authors.initials: JH
authors.lastname: Jeong
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: GonSup
authors.initials: G
authors.lastname: Kim
authors.forename: Jin-Myung
authors.initials: JM
authors.lastname: Jung
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Chung Ho
authors.initials: CH
authors.lastname: Ryu
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Shin
authors.forename: Soon Chan
authors.initials: SC
authors.lastname: Hong
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020014:K562 Cells / Q000187:drug effects; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019697:Onions / Q000737:chemistry*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D059808:Polyphenols / Q000302:isolation & purification / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020169:Caspases; D051034:Inhibitor of Apoptosis Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D059808:Polyphenols; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D044767:Ubiquitin-Protein Ligases; C494833:BIRC2 protein, human
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; 4,6-diamidino-2-phenylindole; Akt; Allium cepa; Apoptosis; DAPI; ELISA; Enzyme-linked immunosorbent assay; FBS; MTT; PBS; PEAL; PI3K; Polyphenols; TNF-related apoptosis-inducing ligand; TRAIL; U937; cIAP; cellular inhibitor of apoptosis; fetal bovine serum; phosphate-buffered saline; phosphatidylinositol 3-kinase; polyphenols extracted from lyophilized Allium cepa Linn