GROUNDS OF A CONJUGATED META-NITROBENZALDEHYDE OF THIOSEMICARBAZONE, A RIBONUCLEOTIDE REDUCTASE AS A ROS GENERATOR AND APOPTOSIS INDUCER IN A549 NON-SMALL CELL LUNG CANCER CELL

Lung cancer is one of the primary causal agents of destruction among all diseases. More than 80% of lung cancer cases are non-small cell lung cancer (NSCLC) cases remaining 20% of lung malignant neoplastic disease are small cell lung cancer (SCLC). In search of potential therapeutics for cancer, we described herein the synthesis, characterization and in vitro anticancer activity of Meta-Nitrobenzaldehydethiosemicarbazone (M-NBTSC).Meta-Nitrobenzaldehydethiosemicarbazone is an interesting case of organic crystal. It has been grown by slow evaporation solution growth technique (SESGT) using wood alcohol as solvent. The MTT assay was applied to determine the IC50 values on A549 lung cancer cell line by M-NBTSC. Features of apoptosis were observed by AO/EB and Hoechst staining. The caspase activity, Bcl-2 family, p21 and p53 proteins were measured by RT-PCR and Western Blot analysis. The M-NBTSC significantly inhibited the growth of A549 cells and induced apoptosis. The M-NBTSC was the most potent on A549 cell line with the IC50 value of 50.50% cell viability 6?g/mL.The induction of apoptosis was overserved by chromosomal condensation, cell shrinkage, membrane blebbing and nuclear fragmentation. The answers showed that M-NBTSC induced apoptosis were associated with an upregulation of proapoptoticBax and down regulation of Bcl2, dissipation of mitochondrial membrane potential and activation of caspase-3. In addition to diminished mitochondrial membrane potential and overproduction of ROS demonstrated the involvement of apoptosis. Mechanistic studies further revealed that M-NBTSC caused the growth of the intracellular ROS, consequently provoked the increase in p21and p53 expression and led to upregulation of Bax, depolarization of mitochondrial membrane potential and caspases cascade (caspase-3/8 and -9). The increase of p53 level by M-NBTSC results in the inhibition of Ribonucleotidereductase (RR) enzymes and stimulates programmed cell death. In this survey suggest that M-NBTSC induces apoptosis through ROS-dependent and induce a potential healing effect for lung cancer.