title: Growth inhibition effects of isoalantolactone on K562/A02 cells: caspase-dependent apoptotic pathways, S phase arrest, and downregulation of Bcr/Abl.
abstract: Isoalantolactone, a sesquiterpene lactone, is the active component of Inula helenium (Compositae). It has been reported that isoalantolactone has the capacity to inhibit tumor cell growth through induction of apoptosis. The purposes of this study were to evaluate the effects of isoalantolactone on the human erythroleukemia drug-resistant cell line K562/A02 and to provide evidence of its function as a potent therapeutic agent in patients with chronic myelogenous leukemia with the Bcr/Abl phenotype. Our results showed that isoalantolactone significantly inhibited K562/A02 cell growth by downregulating Bcr/Abl expression. Isoalantolactone also induced apoptosis via increase generation of reactive oxygen species, modulation of the protein levels of Bcl-2 family members, caspase activation, poly ADP-ribose polymerase (PARP) cleavage, and release of cytochrome c. We also observed that isoalantolactone inhibited proliferation by inducing cell cycle arrest in the S phase. Taken together, all these findings support that growth inhibition effects of isoalantolactone on K562/A02 cells may be mediated through caspase-dependent apoptotic pathways, S phase arrest, and downregulation of Bcr/Abl.
authors.affiliation: Clinical Laboratory, The Second Hospital of Dalian Medical University, Dalian, 116023, PR China; Clinical Laboratory, Shengjing Hospital of China Medical University, Shenyang, 110004, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cai
authors.forename: Xiuxiang
authors.initials: X
authors.lastname: Meng
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Li
authors.forename: Chuihui
authors.initials: C
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D020014:K562 Cells; D053078:Membrane Potential, Mitochondrial; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016196:S Phase / Q000187:drug effects*; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D045304:Cytochromes c; C032787:isoalantolactone; D011065:Poly(ADP-ribose) Polymerases; D016044:Fusion Proteins, bcr-abl; D020169:Caspases
keywords: Bcr/Abl; K562/A02; apoptosis; isolantolactone; proliferation