title: Chaperones are the target in aloe-emodin-induced human lung nonsmall carcinoma H460 cell apoptosis.
abstract: Our previous study has demonstrated that aloe-emodin induced a significant change in the expression of apoptosis-related proteins in H460 cells. However, the molecular mechanisms underlying the biological effects of aloe-emodin still remain unknown. The present study applied 2D electrophoresis (pH range 4-7) to the proteins involved in aloe-emodin (40 muM)-induced H460 cell apoptosis. Eleven proteins were found to markedly change. These altered proteins were identified as ATP synthase, vimentin, HSP60, HSP70 and protein disulfide isomerase. Aloe-emodin caused a time-dependent decrease in intracellular ATP levels, which might be related to direct inhibition of ATP synthase. We also observed that the activity of mitochondria was injured by aloe-emodin. These data clearly demonstrated that mitochondria may play a critical role in aloe-emodin-induced H460 cell death. Many reports emphasize that chaperones have a complex role in apoptosis. The present study suggested that the increasing protein expression of HSP60, HSP70, 150 kDa oxygen-regulated protein and protein disulfide isomerase is involved in aloe-emodin-induced H460 cell apoptosis. HSP70, 150 kDa oxygen-regulated protein and protein disulfide isomerase are endoplasmic reticulum chaperone. Therefore, we hypothesized that the increasing endoplasmic reticulum stress serves to promote H460 cell apoptosis after treatment with aloe-emodin. We also demonstrated aloe-emodin-induced H460 cell death through caspase-3 apoptotic pathway, but not apoptosis-inducing factor apoptotic pathway.
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Miao-Ying
authors.initials: MY
authors.lastname: Lai
authors.forename: Mann-Jen
authors.initials: MJ
authors.lastname: Hour
authors.forename: Henry
authors.initials: H
authors.lastname: Wing-Cheung Leung
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Yang
authors.forename: Hong-Zin
authors.initials: HZ
authors.lastname: Lee
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000880:Anthraquinones / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000880:Anthraquinones; D051033:Apoptosis Inducing Factor; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; C518327:aloe emodin; D007770:L-Lactate Dehydrogenase; D019704:Protein Disulfide-Isomerases