title: Lysosomal membrane permeabilization contributes to elemene emulsion-induced apoptosis in A549 cells.
abstract: Elemene is a broad-spectrum antitumor agent. In the present study, lysosomal membrane permeabilization (LMP) was detected after short elemene emulsion--exposure (12 h) that preceded a decrease of the mitochondrial membrane potential and DNA damage (24 h) in A549 cells. At later time points (36 h) elemene emulsion caused the appearance of A549 cells with apoptotic features, including apoptotic morphology, phosphatidylserine exposure, and caspase-3 activation. A significant increase in protein expression for cathepsin D was also observed utilizing Western blot analysis after exposure to elemene emulsion for 12 h. The present study showed that elemene emulsion induced the increased levels of reactive oxygen species (ROS) and depletion of glutathione (GSH) in A549 cells. Cells treated with pepstatin A, an inhibitor for cathepsin D, showed a significant inhibition in DNA damage, mitochondrial membrane permeabilization, caspase-3 activation, and phosphatidylserine exposure. These results demonstrated that apoptosis induced by elemene emulsion in A549 cells is mediated in part through LMP and lysosomal protease cathepsin D.
authors.affiliation: Department of radiotherapy oncology, 2nd Affiliated Hospital of Dalian Medical University, 467 Zhong Shan Road, Dalian 116023, Liaoning, China.
authors.forename: Long-Jie
authors.initials: LJ
authors.lastname: Li
authors.forename: Lai-Fu
authors.initials: LF
authors.lastname: Zhong
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jiang
authors.forename: Cheng-Yan
authors.initials: CY
authors.lastname: Geng
authors.forename: Ting-Zhun
authors.initials: TZ
authors.lastname: Zhu
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Xu
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Qu
authors.forename: Jing
authors.initials: J
authors.lastname: Shao
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Zou
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002402:Cathepsin D / Q000037:antagonists & inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010436:Pepstatins / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D010436:Pepstatins; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C038905:elemene; D053148:Caspase 3; C533922:CTSD protein, human; D002402:Cathepsin D; D005978:Glutathione; C031375:pepstatin