N-methylformamide as a potential therapeutic approach in colon cancer.

Abstract

The effect of N-methylformamide, used in combination with the antineoplastic drugs adriamycin and cisplatin, on the cell survival of a colon carcinoma cell line (HT-29) was investigated. To better understand the mechanism involved in N-methylformamide-mediated chemosensitization, we evaluated the N-methylformamide effect on cell volume and surface expression of some integrins molecules (VLA2, VLA5, and VLA6) of the HT-29 cell line. The cell survival was evaluated by clonogenic assay; integrins surface expression was analyzed by means of flow cytometry; cell volumes were determined using a Coulter Channalyzer. A Noncytotoxic dose of N-methylformamide (170 mM) sensitizes the HT-29 cell line to the lethal activity of both adriamycin and cisplatin. The analysis of cell volume showed that N-methylformamide exposure induces an increase in cell volume. Flow cytometric analysis of VLA2, VLA5, and VLA6 receptors showed that N-methylformamide increases the expression of the three integrins by 30 to 40 percent. The plasma membrane could constitute one of the N-methylformamide targets and might be involved in the differentiation and chemosensitizing effects caused by this agent. Moreover, N-methylformamide could improve colon cancer treatment when used in combination with antineoplastic drugs.