N-METHYLFORMAMIDE AS A POTENTIAL THERAPEUTIC APPROACH IN COLON-CANCER

PURPOSE: The effect of N-methylformamide, used in combination with the antineoplastic drugs adriamycin and cisplatin, on the cell survival o f a colon carcinoma cell line (HT-29) was investigated. To better unde rstand the mechanism involved in N-methylformamide-mediated chemosensi tization, 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. METHODS: The cell survival was evaluated by c lonogenic assay; integrins surface expression was analyzed by means of flow cytometry; cell volumes were determined using a Coulter Channaly zer. RESULTS: A Noncytotoxic dose of N-methylformamide (170 mM) sensit izes 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 increa ses the expression of the three integrins by 30 to 40 percent. CONCLUS ION: The plasma membrane could constitute one of the N-methylformamide targets and might be involved in the differentiation and chemosensiti zing effects caused by this agent. Moreover, N-methylformamide could i mprove colon cancer treatment when used in combination with antineopla stic drugs.