title: Lysosomal membrane permeabilization is involved in curcumin-induced apoptosis of A549 lung carcinoma cells.
abstract: We previously reported that curcumin inhibited lung cancer A549 cells growth and promoted cell apoptosis in vitro. In this study, we further examined the apoptosis-related parameters, including lysosomal damage and cathepsin activation, in A549 cells exposed to curcumin. We found that curcumin caused lysosomal membrane permeabilization (LMP) and cytosolic relocation of cathepsin B (cath B) and cathepsin D (cath D). However, only Z-FA-fmk (a cath B inhibitor) but not pepstatin A (a cath D inhibitor) inhibited curcumin-induced cell apoptosis, mitochondrial membrane potential loss, and cytochrome c release. The antioxidant N-acetylcysteine and glutathione attenuated LMP, suggesting that lysosomal destabilization was dependent on the elevation of reactive oxygen species and which precedes mitochondrial dysfunction. These findings indicated a novel pathway for curcumin regulation of ROS-lysosomal-mitochondrial pathway and provided the key mechanism of regulation of LMP in cell apoptosis, which may be exploited for cancer treatment.
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Hang Zhou, 310013, People's Republic of China.
authors.forename: Qing-Yong
authors.initials: QY
authors.lastname: Chen
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Shi
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Yao
authors.forename: De-Min
authors.initials: DM
authors.lastname: Jiao
authors.forename: Yan-Yi
authors.initials: YY
authors.lastname: Wang
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Hu
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wu
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects*; D002401:Cathepsin B / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D045304:Cytochromes c; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008247:Lysosomes / Q000648:ultrastructure*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D017382:Reactive Oxygen Species
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D002401:Cathepsin B; D002402:Cathepsin D; D003474:Curcumin