Abstract 62P
Background
Lung cancer is one of the leading contributors of cancer related mortalities worldwide. Out of all the lung cancer cases non-small cell lung cancer (NSCLC) accounts for approximately 80% of overall cases diagnosed. Quinacrine (QC), a synthetic drug belonging to the 9-aminoacridine another name mepacrine, repurposing quinacrine as an anticancer agent appears to be a promising strategy based on its ability to target multiple pathways.
Methods
Human lung cell lines A549 and NCI H520 were cultured for this study. Cytotoxicity of QC was assessed using resazurin dye. Cell cycle analysis was carried out using FACS. Mitochondrial membrane potential activity was analysed using JC-1 activity kit. RT-PCR analysis was carried out to evaluate the profile of various genes at their m-RNA level. Western blotting was performed using various antibodies. Microscopic analysis was carried out to understand the nuclear architecture, along with ROS estimation. GST assay kit was used for analysing GST activity.
Results
NSCLC cells adapt to the chemotherapeutics. through altering numerous cellular pathways along with enhanced activity of enzymes such as GST, MTs including altering various signalling cascades. Through our study we have discovered novel binding of quinacrine with GSTA1 and inhibiting its catalytic activity. This finding has been accompanied with detailed study of the downstream effects of this molecule and novel interaction on viability of cancer cells, cell cycle progression and apoptotic signalling cascade among two non-small cell lung cancer cell lines namely A549 and NCI H520. We have shown that quinacrine causes generation of reactive oxygen species (ROS) leading to ER stress and mitochondria mediated cell death.
Conclusions
Through a detailed study we have finally established that QC inhibited the activity of GSTA1 which inhibits cell survival and promotes apoptosis. QC possesses the advantage of targeting multiple signalling pathways via activation of apoptotic signalling cascades. Our findings add promising value to its expanding horizon of antineoplastic potential, which could be further utilized in designing combinational therapies for better and targeted destruction of NSCLC with fewer side effects.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
This study was funded by the Department of Biotechnology, Govt. of India grant no.-6242-P59/RGCB/PMD/DBT/ANSR/2015 along with a supporting grant from ‘Goa Cancer Society’, Goa, India.
Disclosure
The author has declared no conflicts of interest.
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