Ramesh B Badisa1, David A Mina2, Lekan M Latinwo3, Karam F A Soliman2. 1. College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL, U.S.A. badisa66@gmail.com. 2. College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL, U.S.A. 3. Department of Biology, Florida Agricultural and Mechanical University, Tallahassee, FL, U.S.A.
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. MATERIALS AND 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. CONCLUSION: MPP(+) possesses highly selective, potent anticancer activity against lung adenocarcinoma. Copyright
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 humanlung adenocarcinoma A549, human normal lung and rat normal liver cells after a 48-h treatment. MATERIALS AND 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. CONCLUSION:MPP(+) possesses highly selective, potent anticancer activity against lung adenocarcinoma. Copyright
Authors: Sampath Ramachandiran; Jason M Hansen; Dean P Jones; Jason R Richardson; Gary W Miller Journal: Toxicol Sci Date: 2006-10-03 Impact factor: 4.849
Authors: Ramesh B Badisa; Selina F Darling-Reed; Patrick Joseph; John S Cooperwood; Lekan M Latinwo; Carl B Goodman Journal: Anticancer Res Date: 2009-08 Impact factor: 2.480