title: [Lonidamine induces apoptosis via endoplasmic reticulum stress response and down-regulating cIAP expression in human breast carcinoma MCF-7 cells].
abstract: OBJECTIVE
  To investigate the effect of lonidamine on apoptosis of human breast carcinoma cells MCF-7 and the possible mechanisms.
  
  
  METHODS
  MTT assay and colony-forming assay were used to evaluate the growth inhibition induced by lonidamine in breast cancer MCF-7 cells. PI/Annexin-V staining was used to detect the apoptotic cells. The ATP levels in the cells were detected using an ATP assay kit. The expression of glucose regulated protein 78 (GRP78), inhibitor of apoptosis protein (cIAP1) and caspase-8 were analyzed with Western blotting.
  
  
  RESULTS
  MTT assay and colony-forming assay showed that 50-250 mmol/L lonidamine caused a time- and concentration-dependent inhibition of MCF-7 cell proliferation. Exposure to increased concentrations of lonidamine resulted in significantly increased apoptosis rate in MCF-7 cells. In MCF-7 cells treated with 50, 150 and 250 mmol/L lonidamine for 5 h, the intracellular ATP levels were lowered to 80.67%, 62.78% and 30.73% of the control level, respectively. Western blotting showed that lonidamine up-regulated the expression of GRP78, down-regulated the expression of cIAP1 and promoted caspase-8 activation as the treatment time extended.
  
  
  CONCLUSIONS
  Lonidamine can inhibit the proliferation and induce apoptosis in MCF-7 cells, and these effects are probably mediated by reducing ATP level, inducing endoplasmic reticulum stress response, down-regulating cIAP1, and promoting caspase-8 activation in the cells.
authors.affiliation: School of Nursing, Anhui University of Chinese Medicine, Hefei 230038, China. E-mail: sfr2008@163.com.
authors.forename: Furong
authors.initials: F
authors.lastname: Shao
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Chu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D053181:Caspase 8 / Q000378:metabolism; D049109:Cell Proliferation; D015536:Down-Regulation; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D061986:MCF-7 Cells / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D007191:Indazoles; D051034:Inhibitor of Apoptosis Proteins; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases; C505530:CASP8 protein, human; D053181:Caspase 8; C016371:lonidamine