title: Corosolic acid induces apoptotic cell death in human lung adenocarcinoma A549 cells in vitro.
abstract: Corosolic acid (CRA), a triterpenoid from medicinal herbs, has been shown to induce apoptosis in several cell lines, with the exception of A549 cells. In this report, we investigated the apoptotic effect and mechanism of CRA in A549 cells. The present study shows that CRA significantly inhibits cell viability in a concentration- and time-dependent manner. Exposure to CRA induces sub-G1 cell cycle arrest and causes apoptotic death in A549 cells. CRA also triggers the activation of caspases and poly(ADP-ribose) polymerase, an effect antagonized by z-vad-fmk. In addition, exposure to CRA leads to a significant increase in the levels of reactive oxygen species (ROS) in A549 cells. Furthermore, exposure to the ROS scavenger N acetylcysteine (NAC)prevents CRA-induced apoptosis, suggesting a role for ROS in CRA-induced apoptosis. ROS are critical regulators of caspase-mediated apoptosis in A549 cells. These results indicate that CRA induces mitochondria-mediated and caspase-dependent apoptosis in A549 cells by altering anti-apoptotic proteins in a ROS-dependent manner.
authors: Basic Herbal Medicine Research Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
authors: Kyoung Jin
authors: KJ
authors: Nho
authors: Jin Mi
authors: JM
authors: Chun
authors: Ho Kyoung
authors: HK
authors: Kim
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009842:Oligopeptides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D017382:Reactive Oxygen Species; D014315:Triterpenes; C427308:benzoylcarbonyl-valyl-aspartyl-valyl-alanyl-aspartyl-fluoromethyl ketone; C113861:corosolic acid; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C505520:CASP7 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053179:Caspase 7; D053181:Caspase 8; D053453:Caspase 9