Royal Jelly and Trans-10-Hydroxy-2-Decenoic Acid Inhibit Migration and Invasion of Colorectal Carcinoma Cells
1Department for Biology and Ecology, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, Serbia
2Institute for Information Technologies, Department of Natural Sciences, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia
3Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia
4Department for Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, Serbia
Received: 6 September 2021
Accepted: 12 January 2022
colorectal cancer, EMT, dietary supplement, migration, Snail, trans-10-hydroxy-2-decenoic acid
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 MTT test in concentration range: 1-500 μg/mL after 24 and 72 h. Effects on collective and single cell migration was done by Wound healing and Transwell assay. Invasive potential of cancer cells was evaluated by modified Transwell method with collagen. Immunofluorescence was used for migratory and invasive protein expression, while the gene expression of these markers was evaluated by qRT-PCR. All assays were applied on 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, concentration 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 motility and invasiveness of colorectal cancer cells was observed. More pronounced effect was exerted by 10H2DA that 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 β-catenin in HCT-116 cells, thus stabilizing intercellular connections. In SW-480 cells, 10H2DA increased E-cadherin on protein and gene level, and suppressed 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 hereafter for the first time indicating that these natural products are valuable source of anticancer potential and should be reconsidered for further antitumor therapy.