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Small cell lung carcinoma (SCLC) is a highly aggressive cancer with low survival rate.Although initial response to chemotherapy in SCLC patients is well-rated, the treatments applied after the disease relapses are not successful. Drug resistance is accepted to be one of the main reasons for this failure. Therefore, there is an urgent need for new treatment strategies for SCLC. Meclofenamic acid, a nonsteroidal antiinflammatory drug, has been shown to have anticancer effects on various types of cancers via different mechanisms. The aim of this study was to investigate the alterations that meclofenamic acid caused on a SCLC cell line, DMS114 using the tools of proteomics namely two-dimensional gel electrophoresis coupled to MALDI-TOF/TOF and nHPLC coupled to LC-MS/MS. Among the proteins identified by both methods, those showing significantly altered expression levels were evaluated using bioinformatics databases, PANTHER and STRING. The key altered metabolism upon meclofenamic acid treatment appeared to the cellular energy metabolism. Glycolysis was suppressed, whereas mitochondrial activity and oxidative phosphorylation were boosted. The cells underwent metabolic reprogramming to adapt into their new environment for survival. Metabolic reprogramming is known to cause drug resistance in several cancer types including SCLC. The identified differentially regulated proteins in here associated with energy metabolism hold value as the potential targets to overcome drug resistance in SCLC treatment.

Background/Aim: During the last two decades, Parkinson's disease (PD)-associated genes have been associated with cancer; however, a shared pathogenic mechanism has yet to be discovered. Parkin, an E3 ubiquitin ligase that is involved in early-onset Parkinson's disease, has also been reported to exert tumor suppressor activity. However, the details about the role of Parkin in cancer remain unknown. The present study aimed at identifying differentially regulated nuclear proteins and nuclear phosphoproteins whose levels were affected by Parkin expression. Materials and Methods: SHS-SY5Y cells expressing either wild-type Parkin or its mutant under tetracycline control were used in this study; cells not expressing Parkin served as control. Nuclear proteins were enriched from Parkin-expressing and control cells to perform a comparative proteomics study using two-dimensional gel electrophoresis (2D) coupled to matrix assisted laser desorption/ionisation-time of flight (MALDI-TOF/TOF) mass spectrometry analysis. Changes in phosphoproteome and nuclear phosphoproteome were also studied by staining the 2D gels with ProQ diamond phosphoprotein stain. The identified proteins were subjected to bioinformatics analysis to elucidate the reactomes and relevant pathways. Results: Six nuclear proteins, namely NCL, DDIT3, PARP1, HMGB1, TCTP and TPI were shown to be differentially regulated in cells expressing Parkin protein. Regulations in phosphorylation levels of ENPL, PRDX4, ECHM, ALDOA SET, DHSA, RCC1 and DULRD were also detected. Bioinformatics analysis of differentially regulated proteins highlighted the involvement of Parkin in DNA repair. Conclusion: Several nuclear protein candidates whose expression or phosphorylation levels were altered in cells expressing Parkin. Bioinformatics analysis of these proteins indicated that the nuclear form of Parkin may play a significant role in DNA repair and contribute to prevention of tumorogenesis via maintaining DNA integrity.

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