Investigation of potential inhibitory effects of natural compounds from Melissa officinalis L. in drug-resistant non-small cell lung carcinoma

In cancer treatment, the development of new generation drugs and innovations in surgery have significantly extended the life expectancy of patients. However, despite all these developments, the main obstacle in the treatment of lung cancer is the recurrence of the disease over time due to intrinsic or extrinsic resistance to the chemotherapeutic drugs used in the treatment. Alternative methods and new therapeutics are needed to cope with the development of chemoresistance. Due to their low cytotoxicity and good tolerability in the human body, natural plant compounds are very important sources that can be used to obtain drug active ingredients that have been used in the treatment of many diseases, including cancer, for many years. In this study, the anticarcinogenic effects of Melissa officinalis L., a well-known medicinal plant from the Lamiaceae family, widely grown in Turkey and known as lemongrass, on the non-small cell lung cancer cell line A549 and the erlotinib resistant A549 sub-cell line and its parallel parental sub cell-line were evaluated. In our study, four different extracts were obtained from the leaf parts of Melissa officinalis L. plant with different solvents. The cytotoxic effects of these extracts on each cell line were determined by MTT cell viability analysis. As a result, although each type of extract was cytotoxic on each sub-cell line, there was no significant difference between their inhibitory intensities. The remainder of the study was then continued with the total methanolic fraction, which includes all of the substance groups in the plant leaf. Afterwards, the effects of this extract on the migration of different sub-cell lines were determined by the wound healing assay, whereas tumorigenic capacities were determined by the soft agar colony formation test. Finally the effects of the total methanolic extract on the cell cycle progression were determined by flow cytometry analysis. According to the results, increasing concentration of total MeOH extract of M. officinalis L. decreases cell viability in a concentration dependent manner and prevents both migration capacity and colony formation in all types of sub-cell lines. A decrease was observed in the S-phase cell populations, where DNA replication takes place, compared to cells exposed to control in all three sub-cell lines. In the light of these findings, it is thought that Melissa officinalis L. plant may represent an alternative source of novel therapeutic compounds for treatment of non-small cell lung cancer. Keywords: Melissa officinalis L. , natural compounds, A549, anticancer , drug resistance