title: Selective anticancer activity of neurotoxin 1-methyl-4-phenylpyridinium on non-small cell lung adenocarcinoma A549 cells.
abstract: BACKGROUND
  Lung cancer is the second leading cause of mortality among men and women in the U.S. Among different varieties of lung cancer, the non-small cell lung cancer (NSCLC) has the highest frequency comprising about 85% of cases. We evaluated 1-methyl-4-phenylpyridinium ion (MPP(+)) for cytotoxicity against human lung adenocarcinoma A549, human normal lung and rat normal liver cells after a 48-h treatment.
  
  
  METHODS
  In vitro cytotoxicity was evaluated by the crystal-violet method, mitochondrial respiratory status by calorimetric reduction of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, mitochondrial membrane potential by rhodamine 123 fluorometric assay and glutathione levels by 5,5-dithiobis-2-nitrobenzoic acid.
  
  
  RESULTS
  MPP(+) caused a significant dose-dependent death of A549 cells. In human normal lung and rat normal liver cells, MPP(+) did not cause severe cytotoxicity, which was reflected with a selectivity index (SI) of greater than 7. Further studies revealed that, in addition to its interaction with mitochondria, MPP(+) significantly depleted total glutathione levels in A549 cells.
  
  
  CONCLUSIONS
  MPP(+) possesses highly selective, potent anticancer activity against lung adenocarcinoma.
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL, U.S.A. badisa66@gmail.com.
authors.forename: Ramesh B
authors.initials: RB
authors.lastname: Badisa
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL, U.S.A.
authors.forename: David A
authors.initials: DA
authors.lastname: Mina
authors.affiliation: Department of Biology, Florida Agricultural and Mechanical University, Tallahassee, FL, U.S.A.
authors.forename: Lekan M
authors.initials: LM
authors.lastname: Latinwo
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL, U.S.A.
authors.forename: Karam F A
authors.initials: KF
authors.lastname: Soliman
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D005978:Glutathione; D015655:1-Methyl-4-phenylpyridinium
keywords: 1-methyl-4-phenylpyridinium ion; Anticancer activity; glutathione; human non-small cell lung adenocarcinoma cells; selectivity index