# Comparison of the Biological Potential and Chemical Composition of Brazilian and Mexican Propolis
## 3 Discussion
### Antiproliferative and Cytotoxic Activity  
Propolis cytotoxic activity has been extensively studied, particularly in cancer research [119]. The chemical composition of propolisis is well known and quite varied. Some compounds found in different types of propolisis have been reported and associated with cytotoxic activity [120; 121]. This cytotoxic and antiproliferative activity against tumor cells may not be due to isolated compounds nonetheless to the synergism between all the compounds in propolisis [98]. Many of these compounds that are associated with these activities have previously been identified with antioxidant capabilities [122]. Figures showing the comparison of the cell lines used in researches carried out with Brazilian propolisis are presented (Figure 6A,B). A greater variety of cell types was observed where the cytotoxicity of the extracts was tested, especially the cells of the reproductive system (\(\approx\)40%). Among the articles verified, more than 80% of the cytotoxicity tests with the different cells were carried out with different types of extracts (ethanolic and supercritical) of red propolisis, originating from the northeast region of Brazil (SE, AL, BA, RN). As mentioned before, in the last decade, studies with this type of propolisis gained notoriety. The most used cell lines in the tests were HCT-116, OVCAR-8, SF-295, HL-60, PC3 [50; 64; 123; 124; 125]. In studies related to the use of Mexican propolis extracts (Figure 7A,B) with cytotoxic activity, it appears that most of the research was carried out on murine cells (40%) and cells of the reproductive system (40%). The M12.C3.F6 murine cell line was the most used on tests. Altiplano region propolis was its effectiveness proven compared with anti-cancer drugs and show an antiproliferative effect on glioma cells better than temozolomide, despite this proliferation and viability in cervical cancer cells (HeLa, SiHa, and CaSki) is lower than cisplatin [41]. The method used in the study was the MTT test, being this the most frequently used test to analyze the metabolic activity of a cell and evaluate its cytotoxic activity. In the northern region of Mexico, murine B cell lymphoma (M12.C3.F6 cancer cell line) has been reported to evaluate the antiproliferative activity on cancer cells in Sonora desert propolis due to its high sensitivity to anti-cancer drugs [57, 137, 138] having excellent results. It has been proven that propolis and its components show proapoptotic activity inducing extrinsic and intrinsic pathways for cell apoptosis [119]. However, desert propolis samples showed a low antiproliferative activity on the murine normal cell line L-929, demonstrating that propolis shows a much lower antiproliferative effect in murine non-cancerous than in murine cancerous cell lines [137]. Another main result is that the antiproliferative effect is affected by quantitative fluctuations in its desert propolis polyphenic profile due to its collection time [138, 139]. Sonora desert propolis has been extensively studied by [PERSON] et al. [140, 141]. Results showed more cytotoxicity against human lung adenocarcinoma (A549 cells) than with other five cancer cell lines, and PANC-1 human pancreatic cancer cells observed resolute preferential cytotoxic activity with similar results in propolis from Brazil [126]. The compounds with potent and preferential toxicity in PANC-1 is (6 aR,11 aR)-3.8-dihydroxy-9-methoxy-9-methoxy-9-methoxy-9-methoxy-9-methoxy-9-methoxy-9-methoxy-9-methoxy-9-methoxy-9  
The antiproliferative effect of propolisols extracts generally depends on their chemical composition, as described above. Chemical compounds present in various types of propolis, to which biological activities are related, could act as powerful cytocidal effects and induced levels of apoptosis in all the cellular lines [122, 143, 144, 145].