## 3 Results and Discussion
### Cytotoxic/Proliferative Effect of Mountain Germander Extract on Human Cell Lines  
One of the most important indicators of the biological activity of a target compound or a mixture of bioactive compounds is the property of a cytotoxic or proliferative effect on certain cell lines, which depends on the concentration applied and the duration of treatment. A statistically significant (\(p<0.05\)) decrease in viable cells, i.e., a cytotoxic effect, was observed in Caco-2 and AGS after prolonged treatment (24 h) for all concentrations of MG extract (0.025, 0.050, 0.150, and 0.500 mg mL\({}^{-1}\)) (Figure 4). On the other hand, [PERSON] et al. (2011) [27] found a dose-dependent cytotoxic effect of the methanolic MG macerate in the concentration range of 0.050-1 mg mL\({}^{-1}\) on HCT-116 colon cancer cells. Using the MTT assay, a significant cytotoxic effect (\(p<0.05\)) of the extract was observed after 24 h of treatment at all concentrations. However, prolonged treatment (72 h) at the lowest applied concentration of the extract (0.050 mg mL\({}^{-1}\)) resulted in the strong proliferative effect. When comparing results, a much longer exposure time, methanol as the extraction solvent, the cell line type, and the applied assay for cytotoxicity determination should be considered. Furthermore, in the work of [PERSON] et al. (2015) [20], human melanoma cells (Fem-x), human breast cancer cells (MDA-MB-361), chronic myeloid leukemia cells (K562), and cervical adenocarcinoma cells (HeLa) were treated with the same prepared MG extract. A pronounced dose- and cell line-dependent cytotoxic effect of the tested extract in the range of 0.0125-0.200 mg L\({}^{-1}\) was observed. The highest concentration of the extract had the strongest antitumor effect on K562 and HeLa cells, reducing their viability by ~97% and ~85%, respectively, during 72 h at a concentration of 0.200 mg L\({}^{-1}\). In addition, it is important to mention the results of the treatment of human normal immunocompetent blood cells (PBMC) and proliferation-stimulated blood cells (PBMC-PHA) with phytohemagglutinin (conditions the coagulation of leukocytes) in the same work with the same concentration of MG extract, whereby the viability of the tested cells was reduced by 20% only for PBM-PHA, which indicates the selectivity of the polyphenol extract towards certain cell lines, and thus modulates the antitumor effect. The cytotoxic effect of the MG extract on AGS, Caco-2, and HepG2 cells at the highest concentration and during the 24 h of exposure may be partly related to the presence of phenylethanolamine glycosides, which account for about 22% of the freeze-dried MG extract used in this study, with echinacoside representing approximately 40% of the total. In the study by [PERSON] et al. (2019) [49], a significant increase in antiproliferative activity by increasing the concentration of echinacoside (20 ug mL\({}^{-1}\)--9.57%; 50 ug mL\({}^{-1}\)--26.67%; 100 ug mL\({}^{-1}\)--37.20%) on HepG2 cells and myeloid cells was observed. The influence of structurally similar polyphenolic compounds, such as verbascoside, should also not be excluded. For example, [PERSON] et al. (2014) [50] reported a stronger cytotoxic effect of verbascoside (23-30%) compared to echinacoside (10-18%) and calkeolaoriside A (13-18%) and B (5-15%). Additionally, [PERSON] et al. (2018) [51] reported a significant cytotoxic effect of verbascoside in the treated range of 0.01-100 uM on Caco-2 (decreased cell viability by 70%) and HCT-116 (decreased cell viability by 80%) cells, while the combination of a verbascosidedose of 0.1 \(\upmu\)M and 10 \(\upmu\)M fluorouracil as a standard chemotherapeutic agent resulted in a significant synergistic cytotoxic effect (Caco-2: 80%, HCT-116: 90%). Numerous studies also confirm the antiproliferative effect of other plant extracts that are rich in phenylethanol glycosides. For example, [PERSON] et al. (2021) [PERSON] et al.