N-glycan biosynthesis inhibitors induce in vitro anticancer activity in colorectal cancer cells.

During malignant transformation, changes in the expression profile of glycans may be involved in a variety of events, including the loss of cell-cell and cell-matrix adhesion, migration, invasion, and evasion of apoptosis. Therefore, modulation of glycan expression with drugs has promising therapeutic potential for various cancer types. In this study, we investigated the in vitro anticancer activity of the N-glycan biosynthesis inhibitors (swainsonine and tunicamycin) in cells derived from colorectal cancer (CRC). We also examined whether these inhibitors are able to induce radiosensitization and toxicity when used in combination with cisplatin or irinotecan, two current anticancer drugs. Our results show that treatment with tunicamycin inhibits cellular mechanisms related to the malignant phenotype, such as anchorage-dependent and anchorage-independent colony formation, migration and invasion, in undifferentiated HCT-116 colon cancer cells, whereas swainsonine only inhibits cell migration. We also observed that tunicamycin, but not swainsonine, caused radiosensitivity in HCT-116 cells. Moreover, the combination of swainsonine with cisplatin or irinotecan enhanced their toxicity in HCT-116 cells, while the combination of tunicamycin with these drugs had no effect. Given these results, we suggest that the modulation of N-glycan biosynthesis appears to be a potential therapeutic tool for CRC treatment because inhibition of this process induced anticancer activity in vitro. Additionally, the inhibition of the N-glycan biosynthesis in combination with chemotherapic drugs is a promising therapeutic strategy for enhancing radiation therapy.

Similar proteomic profiles of human mesenchymal stromal cells from different donors.

BACKGROUND AIMS: Bone marrow (BM) stromal cells, also referred to as mesenchymal stromal cells (MSC), can be expanded ex vivo and are able to differentiate along multiple lineages, including chondrocytes, osteoblasts and adipocytes. MSC are known to secrete a number of cytokines and regulatory molecules implicated in different aspects of hematopoiesis, and seem to modulate the immune system. MSC appear to be promising candidates for cellular therapy associated with BM transplantation (BMT). METHODS: We compared protein expression profiles of MSC cultures derived from different BM donors using two-dimensional (2-D) gel electrophoresis and matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) tandem mass spectrometry (MS/MS), and compared mixed lymphocyte reaction (MLR) assays in the absence and presence of third-party human (h) MSC derived from different donors during the same culture passage. RESULTS: In a window of observation (pH 4-7, molecular weight 10-220 kDa), about 172 protein spots were obtained in each 2-D gel, corresponding to 84 distinct proteins. A comparative analysis demonstrated a very similar proteomic profile of cells of the first passage derived from different donors, suggesting that these cells have the same expression pattern. Additionally, cells derived from different donors were equally able to inhibit lymphocyte proliferation. CONCLUSIONS: These results encourage the use of third-party MSC in cellular therapies, as cells derived from different individuals seem to have the same proteomic pattern and exhibit functionally similar properties.