Research background. Acquisition of migratory potential is pivotal for cancer cells, enabling invasion and metastasis of colorectal carcinoma. Royal jelly and its bioactive component trans-10-hydroxy-2-decenoic acid (10H2DA) showed remarkable antimetastatic potential, but the molecular mechanism underlying this activity is unclear. Experimental approach. Identification and quantification of 10H2DA in royal jelly originating from Serbia was done by HPLC method. Cytotoxicity of 10H2DA was measured by tetrazolium dye MTT test in concentration range 1-500 mu g/mL after 24 and 72 h. Its effect on the collective and single-cell migration was measured by wound healing and transwell migration assays. Invasive potential of cancer cells was evaluated by a transwell method modified with collagen. Immunofluorescence was used for migratory and invasive protein expression, while the gene expression of these markers was evaluated by quantitative real time polymerase chain reaction (qRT-PCR). All assays were applied on human colorectal carcinoma HCT-116 and SW-480 cell lines and, except for MTT, evaluated after 24 h of treatment with two selected concentrations of royal jelly and 10H2DA. Results and conclusions. According to HPLC, the mass fraction of 10H2DA in royal jelly was 0.92 % (m/m). Treatment with 10H2DA showed no cytotoxic effect; however, significant inhibitory potential of royal jelly and 10H2DA on the motility and invasiveness of colorectal cancer cells was observed. More pronounced effect was exerted by 10H2DA, which significantly suppressed collective cell migration and invasiveness of SW-480 cells, as well as single- and collective cell migration and invasive potential of HCT-116 cell line. Treatments increased epithelial markers E-cadherin and cytoplasmic beta-catenin in HCT-116 cells, thus stabilizing intercellular connections. In SW-480 cells, 10H2DA increased E-cad-herin on protein and gene level, and suppressed epithelial-mesenchymal transition (EMT) markers. In both cell lines, treatments induced significant suppression of promigratory/proinvasive markers: N-cadherin, vimentin and Snail on protein and gene level, which explains decreased migratory and invasive potential of HCT-116 and SW-480 cells. Novelty and scientific contribution. Our study presents new findings and elucidation of royal jelly and 10H2DA molecular mechanism that underlies their antimigratory/antiinvasive activity on colorectal cancer cells. These findings are shown for the first time indicating that these natural products are a valuable source of anticancer potential and should be reconsidered for further antitumour therapy.

Nowadays, biomedicine is a multidisciplinary science that requires a very broad approach to the study and analysis of various phenomena essential for a better understanding of human health. This study deals with the use of numerical simulations to better understand the processes of cancer viability and apoptosis in treatment with commercial chemotherapeutics. Starting from many experiments examining cell viability in real-time, determining the type of cell death and genetic factors that control these processes, a lot of numerical results were obtained. These in vitro test results were used to create a numerical model that gives us a new angle of observation of the proposed problem. Model systems of colon and breast cancer cell lines (HCT-116 and MDA-MB-231), as well as a healthy lung fibroblast cell line (MRC-5), were treated with commercial chemotherapeutics in this study. The results indicate a decrease in viability and the appearance of predominantly late apoptosis in the treatment, a strong correlation between parameters. A mathematical model was created and employed for a better understanding of investigated processes. Such an approach is capable of accurately simulating the behavior of cancer cells and reliably predicting the growth of these cells.

This study provides data about anticancer properties of bee venom and its dominant compound, melittin on colorectal carcinoma cells (HCT-116 and SW-480) in regard to their proapoptotic activity and expression of genes involved in biotransformation process. Based on results, they are strong cytotoxins, where the melittin showed also selectivity against cancer cells compared to normal, HaCat. They induce proapoptotic activity by affecting apoptosis signaling molecules (Fas receptors, caspase 9, and members of Bcl-2 family of proteins) and mainly suppress expression of genes involved in their biotransformation, suggesting their ability to develop the resistance of colorectal cancer cells.

Laetiporus sulphureus (Bull.) Murrill is a well-known edible mushroom consumed in nutrition as delicacy. It has been used in traditional medicine because of its beneficial effects on human wellness, such as antimicrobial, antioxidant, and anticancer potential. The present study determined the phenolic profile of Laetiporus sulphureus ethanolic extract (LSE) by high-performance liquid chromatographic method. Tolerance of two probiotic bacterial strains Lactiplantibacillus plantarum 229v, Bifidobacterium animalis subsp. lactis and probiotic yeast Saccharomyces boulardii on LSE was analyzed in terms of viability and biofilm formation. Effects of extract on colorectal (HCT-116) and cervical (HeLa) cancer cells viability was determined using MTT test in concentration range: 1-500 mu g/mL after 24 and 72 h. Redox parameters (superoxide anion radicals, nitrites, and reduced glutathione) were evaluated using NBT, Griess, and GSH assays in the concentration range of 1-500 mu g/mL after 24 and 72 h. Antimigratory activity was determined by wound healing method using selected concentrations of 10 and 50 mu g/mL after 24 h. Untreated cells were considered as control. As control cell line, we used healthy fibroblasts (MRC-5). Our results demonstrated abundance of LSE in phenolics, with rosmarinic acid as the main component. LSE induced low tolerance of tested planktonic probiotic strains, with no affection on their ability to form biofilm. No significant cytotoxicity on tested cancer cells was observed, with prooxidative and antimigratory effects noticed. Extract exerted significant antimigratory activity on cancer cells without effect on planktonic and probiotic cultures in biofilm. These results indicate potential application of Laetiporus sulphureus ethanolic extract as natural protector of probiotics with prominent ability to suppress cancer cell motility.

(1) Background: Cancer stem cells (CSCs) are a subpopulation of cells in a tumor that can self-regenerate and produce different types of cells with the ability to initiate tumor growth and dissemination. Chemotherapy resistance, caused by numerous mechanisms by which tumor tissue manages to overcome the effects of drugs, remains the main problem in cancer treatment. The identification of markers on the cell surface specific to CSCs is important for understanding this phenomenon. (2) Methods: The expression of markers CD24, CD44, ALDH1, and ABCG2 was analyzed on the surface of CSCs in two cancer cell lines, MDA-MB-231 and HCT-116, after treatment with 5-fluorouracil (5-FU) using flow cytometry analysis. A machine learning model (ML)–genetic algorithm (GA) was used for the in silico simulation of drug resistance. (3) Results: As evaluated through the use of flow cytometry, the percentage of CD24-CD44+ MDA-MB-231 and CD44, ALDH1 and ABCG2 HCT-116 in a group treated with 5-FU was significantly increased compared to untreated cells. The CSC population was enriched after treatment with chemotherapy, suggesting that these cells have enhanced drug resistance mechanisms. (4) Conclusions: Each individual GA prediction model achieved high accuracy in estimating the expression rate of CSC markers on cancer cells treated with 5-FU. Artificial intelligence can be used as a powerful tool for predicting drug resistance.