# Brazilian Propolis: Nature's Liquid Gold with Anti-Inflammatory and Anticancer Potential
## 4 Secondary Metabolites of Brazilian Propolis
Brazilian propolis compounds also make cancer cells more susceptible to chemotherapeutic agents by blocking activation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) [85; 86]. Additionally, by preventing angiogenesis, also known as neovascularization, Brazilian propolis extract may also have anti-tumour effects [88; 89]. This is a multi-step process of developing new blood vessels from existing ones, which is very important in regulating the growth and maintenance of metastatic tumours. This process is very complex and stimulates cell proliferation, migration and invasion, making tumour growth mainly dependent on angiogenesis [88; 90; 89]. In many diseases characterised by persistent abnormal growth of blood vessels, angiogenesis is disturbed or absent. It may be observed in certain types of cancer and inflammatory diseases [88]. Figure 5: Visualization of the potential anti-inflammatory mechanisms of Brazilian propolis (created with BioRender.com). Due to its high content of artepilin C and flavonoids, Brazilian propolis, especially the green variety, has strong anticancer properties. Studies show that it inhibits the proliferation of cancer cells, induces their apoptosis and produces anti-inflammatory and antioxidant effects. It also supports the immune system and may improve the efficacy of cancer treatment while reducing the side effects of chemotherapy and radiotherapy [91; 92]. In a study by [PERSON] et al., Colombian propolisols, rich in phenolic acids and flavonoids, the most representative of which are chrysoeriol-O-methyl-ether, ellagic acid and 3,4-O-dimethylcaffeic acid, showed low levels of cytotoxicity and cell cycle detection in gingival fibroblasts and L929 in the G2/M phase. It may be associated with cytoprotective, proliferative or regenerative effects [93]. [PERSON] et al. demonstrated the cytotoxic effect of Brazilian red propolisols extract on the human colon cancer cell line (HCT-116) with an inhibition rate of more than 90%, while for human leukaemia (HL-60) and human prostate cancer (PC3) cell lines, the minimum value identified was 80%. The authors suggest that the composition of Brazilian red propolis varies considerably depending on its geographical origin and the method of extraction, which determines the resulting compounds in the propolis [10]. [PERSON] et al. demonstrated cytotoxic activity of yellow, red, brown and green Brazilian propolis in relation to three cancer cell lines. The green propolisols extract showed low inhibition of all lines of cancer cell tested, presenting low cytotoxic potential [HL-60, human ovarian cancer (OVCAR-8) and human glioblastoma cancer (SF-295), HCT-116]. In contrast, the ethanolic extract of brown Brazilian propolisols had the highest cytotoxic potential, with an inhibition percentage exceeding 75% in all four cancer cell lines. Yellow Brazilian propolisis extract showed high cytotoxic activity only against OVCAR-8 cancer cells [7]. Numerous studies have confirmed the anticancer effect of propolisols in both in vitro and in vivo models. The studies are presented in Tables 3 and 4 below, and potential pathways of action for the anticancer effect of Brazilian propolis are shown in Figure 6.  
Figure 6: Visualization of the potential anticancer mechanisms of Brazilian propolisis. Created with BioRender.com. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Type of Propolis** & **Class of Compounds** & **Cell Lines** & \begin{tabular}{c} **Concentration/** \\ **I\({}_{\text{SO}}\)** \\ \end{tabular}  & **Activity/Mechanism/Effect** & **Ref** \\ \hline \multirow{4}{*}{ \begin{tabular}{c} **Hydroalcoholic extract** \\ **of brown propolis** \\ \end{tabular}  } & Gallic acid, catechchin, chlorogenic & \multirow{4}{*}{ \begin{tabular}{c} **HulP7.5, A549,** \\ **LLC-MR2** \\ \end{tabular}  } & \multirow{4}{*}{ \begin{tabular}{c} **HulP7.5, A549,** \\ **LLC-MR2** \\ \end{tabular}  } & \multirow{4}{*}{ \begin{tabular}{c} **O.25, 0.5, 1.0, 2.5, 5.0, 10, 25, 50,** \\ **and 100 ug/mL** \\ \end{tabular}