Investigation of synergistic anticancer effects of melissa officinalis plant extract and osimertinib on non-small cell lung cancer cell line

Cancer ranks among the most significant diseases worldwide, affecting millions of people through its various forms and presenting a prognosis that is difficult to generalize. Innovations in surgical approaches and the development of next-generation therapeutics have markedly extended patient survival times. However, intrinsic and acquired resistance to drugs remains one of the major obstacles in cancer treatment. In lung cancer, chemoresistance contributes to disease recurrence and reduced survival rates. Studies addressing chemoresistance have provided substantial evidence suggesting that certain phytochemicals can overcome drug resistance in cancer cells. Due to their relatively low side-effect profiles, plant-derived compounds are receiving growing interest as adjuncts in cancer therapy. Osimertinib is an orally administered, third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that selectively targets the T790M resistance mutation, one of the common activating mutations of EGFR. Melissa officinalis (M. officinalis), owing to its low toxicity, has been widely employed as an adjunct in the long-term treatment of various cancer types and chronic diseases. Numerous studies have demonstrated the anticancer and antiproliferative properties of its essential oil and extracts on various human cancer cell lines, yielding significant findings. This thesis investigated the synergistic effect of aqueous and methanolic extracts of M. officinalis in combination with osimertinib on non-small cell lung cancer (NSCLC) cells under in vitro conditions. Across all tested doses, antagonism was observed. The highest Combination Index (CI) value was calculated as 3031.44 using the Compusyn software, determined at a 48-hour incubation with 50 µg/ml of methanolic extract of M. officinalis and 50 nM of osimertinib. In this most antagonistic combination, the expression levels of certain apoptotic and pro-apoptotic genes were examined, partially elucidating the metabolic mechanisms underlying the observed combinatorial effects.