title: RETRACTED: Maslinic acid induces mitochondrial apoptosis and suppresses HIF-1α expression in A549 lung cancer cells under normoxic and hypoxic conditions.
abstract: The apoptotic effects of maslinic acid (MA) at 4, 8, 16, 32 and 64 μmol/L on human lung cancer A549 cells under normoxic and hypoxic conditions were examined. MA at 4-64 and 16-64 μmol/L lowered Bcl-2 expression under normoxic and hypoxic conditions, respectively (p < 0.05). This agent at 4-64 μmol/L decreased Na+-K+-ATPase activity and increased caspase-3 expression under normoxic conditions, but at 8-64 μmol/L it caused these changes under hypoxic conditions (p < 0.05). MA up-regulated caspase-8, cytochrome c and apoptosis-inducing factor expression under normoxic and hypoxic conditions at 8-64 μmol/L and 32-64 μmol/L, respectively (p < 0.05). MA down-regulated hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), survivin and inducible nitric oxide synthase (iNOS) expression under normoxic and hypoxic conditions at 8-64 and 16-64 μmol/L, respectively (p < 0.05). After cells were pre-treated with YC-1, an inhibitor of HIF-1α, MA failed to affect the protein expression of HIF-1α, VEGF, survivin and iNOS (p > 0.05). MA at 8-64 and 32-64 μmol/L reduced reactive oxygen species and nitric oxide levels under both conditions (p < 0.05). These findings suggest that maslinic acid, a pentacyclic triterpenic acid, exerted its cytotoxic activities toward A549 cells by mediating mitochondrial apoptosis and the HIF-1α pathway.
authors.affiliation: Department of Respiratory Therapy, China Medical University, Taichung 40402, Taiwan.
authors.forename: Te-Chun
authors.initials: TC
authors.lastname: Hsia
authors.affiliation: Department of Nutrition, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Wen-Hu
authors.initials: WH
authors.lastname: Liu
authors.affiliation: Institute of Medicinal Chemistry and Department of Chemistry, East China Normal University, Shanghai 200241, China.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Qiu
authors.affiliation: Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan. mcyin@mail.cmu.edu.tw.
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Yin
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001980:Bronchi / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D000077022:Survivin; D014315:Triterpenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives
chemical_list: D051033:Apoptosis Inducing Factor; D053148:Caspase 3; D053181:Caspase 8; D045304:Cytochromes c; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051034:Inhibitor of Apoptosis Proteins; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D017382:Reactive Oxygen Species; D000254:Sodium-Potassium-Exchanging ATPase; D000077022:Survivin; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; C107489:BIRC5 protein, human; C412811:maslinic acid; D009828:Oleanolic Acid; C496319:NOS2 protein, human