Anti-Mitotic Activity of NSAIDs: Molecular Target Identification
Dept. of Biophysics, MolecularBiology and Bioinformatics, University of Calcutta and Haldia Institute of Technology, 2019
Goal
To evaluate the anti-mitotic activity of Diclofenac and its effect on the identified target, Lactate Dehydrogenase-A (LDH-A).
Contribution
I conducted computational docking studies to assess the interaction of several non-steroidal anti-inflammatory drugs (NSAIDs) with LDH-A. Additionally, I assisted in performing enzyme kinetic assays using UV-Visible spectrophotometry to examine Diclofenac’s interaction with LDH-A. My work also involved investigating Diclofenac’s binding to the aromatic residues of LDH-A through fluorescence quenching techniques. Furthermore, I contributed to studies evaluating the apoptotic effects of Diclofenac on HeLa cervical cancer cells.
Result
In silico analyses revealed that Diclofenac exhibited the highest binding affinity for LDH-A among the NSAIDs tested. This was corroborated by enzyme kinetic assays, which showed a concentration-dependent reduction in LDH-A activity. Fluorescence quenching studies provided further insights into the number and nature of Diclofenac’s binding sites on LDH-A. Moreover, Diclofenac treatment induced a dose-dependent increase in apoptosis in HeLa cells.
Impact
NSAIDs have shown promise as repurposed anti-cancer agents, and Diclofenac stands out as a potential candidate. While the precise mechanism driving Diclofenac’s apoptotic effects was previously unclear, this study offers valuable insights into its interaction with LDH-A and its contribution to cancer cell apoptosis, paving the way for further exploration of its therapeutic potential.
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