ONCOmmunity

Selective anticancer activity of neurotoxin 1-methyl-4-phenylpyridinium on non-small cell lung adenocarcinoma A549 cells.

By: Ramesh B Badisa, David A Mina, Lekan M Latinwo, Karam F A Soliman

College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL, U.S.A. badisa66@gmail.com.
2014-10-3; doi:

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

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.