Synthesis and Characterization of Thymoquinone‐Oxime (TQ‐Ox) from Thymoquinone and Evaluation of its Cytotoxic, Genotoxic, and Apoptotic Potential in Lung Cancer Cells (A549) in vitro

Abstract

AbstractIntro: Thymoquinone(TQ), a compound derived from Nigella sativa, has been found to impede cancer progression, including proliferation, migration, and invasion. Previous research has explored the potential benefits of augmenting TQ with functional groups to enhance its activity, particularly when combined with traditional drugs. The aim of our study was to investigate the therapeutic effects of Thymoquinone‐Oxime(TQ−Ox) on lung cancer cell lines. Methods: To determine the structure of the novel TQ−Ox substance, we employed NMR spectroscopy. We also performed in vitro assays to assess the anti‐cancer mechanisms of TQ−Ox on lung cancer cells(A549) and healthy lung cells(BEAS‐2B). These assays included assessments of cytotoxicity, genotoxicity, and apoptosis, as well as measurements of intracellular Reactive Oxygen Species(iROS), intracellular Calcium(iCa2+), and Mitochondrial Membrane Potential(MMP). Results: Our results demonstrate that TQ−Ox induces dose‐dependent cytotoxicity, genotoxicity, and apoptosis in cancer cells, along with an increase in iROS production. The IC50 values for A549 and BEAS‐2B cells were 41.01 μM and 48.71 μM, respectively. We also observed that as iCa2+ levels increased, there was a decrease in MMP levels(p<0.001). Conclusion: TQ−Ox shows potential as a therapeutic option for lung cancer, justifying further in vitro and in vivo research to explore its clinical applications.