title: N-glycan biosynthesis inhibitors induce in vitro anticancer activity in colorectal cancer cells.
abstract: 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.
authors.affiliation: Divisão de Biologia Celular, Coordenação de Pesquisa, Instituto Nacional de Câncer, 37André Cavalcanti Street, 5th Floor, CEP: 20230-051 Rio de Janeiro, Brazil.
authors.forename: Julio Cesar Madureira
authors.initials: JC
authors.lastname: de-Freitas-Junior
authors.forename: Lilian Golçalves
authors.initials: LG
authors.lastname: Bastos
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Freire-Neto
authors.forename: Bárbara Du
authors.initials: BD
authors.lastname: Rocher
authors.forename: Eliana Saul Furquim Werneck
authors.initials: ES
authors.lastname: Abdelhay
authors.forename: José Andrés
authors.initials: JA
authors.lastname: Morgado-Díaz
mesh_terms: D015153:Blotting, Western; D018938:Caco-2 Cells; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005434:Flow Cytometry; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D000077146:Irinotecan; D011134:Polysaccharides / Q000378:metabolism*; D017026:Swainsonine / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology*
chemical_list: D011134:Polysaccharides; D014415:Tunicamycin; D000077146:Irinotecan; D002945:Cisplatin; D017026:Swainsonine; D002166:Camptothecin