Abstract 393P
Background
Thoracic tumors, including lung cancer and malignant pleural mesothelioma (MM), are leading causes of cancer-related mortality due to their poor 5-year survival rates and limited therapeutic options for advanced stages. Novel therapies with high efficacy and low toxicity are urgently needed. Traditional Chinese Medicine (TCM) offers a holistic approach with unique pharmacological mechanisms and reduced toxicity. This study investigates the therapeutic potential of Narciclasine, a TCM-derived compound, against lung cancer and MM.
Methods
The effects of Narciclasine were assessed in 3D tumor spheroid models derived from lung adenocarcinoma (LUAD) (A549, LuCa1) andMM (MSTO-211H, H2052/484) cell lines. Cellular responses were evaluated through morphological analysis, intracellular adenosine triphosphate (ATPi) measurements, and lactate dehydrogenase (LDH) activity assays. Differential gene and protein expression related to ferroptosis and cuproptosis pathways were analyzed using RT-qPCR and western blotting. In silico target prediction identified shared molecular targets across cancer types.
Results
Narciclasine significantly inhibited tumor spheroid viability, with a pronounced effect in MM spheroids, achieving an 80% reduction. IC50 values ranged from 50 to 150 nM, demonstrating potent activity. Narciclasine induced cell apoptosis and suppressed proliferation, particularly in MM. It modulated key regulators of ferroptosis and cuproptosis pathways. In silico analysis revealed 308 targets shared between Narciclasine and lung cancer, 62 with mesothelioma, and 61 overlapping targets for both malignancies.
Conclusions
Narciclasine, a TCM compound, shows promising efficacy against lung cancer and MM, with a mechanistic basis in ferroptosis and cuproptosis pathways. Its in silico molecular target profile supports its potential as a therapeutic candidate. These results highlight the need for further investigation into the mechanisms of action and potential clinical applications of Narciclasine for treating thoracic malignancies, offering hope for improved therapeutic options and patient outcomes.
Funding
Fondation Ernest Boninchi
Disclosure
The author has declared no conflicts of interest.