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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Del Bufalo
D
D
Laboratory of Experimental Chemotherapy, Regina Elena Institute for Cancer Research, Rome, Italy.
Bucci
B
B
D'Agnano
I
I
Zupi
G
G
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002470:Cell Survival; D002945:Cisplatin / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D005434:Flow Cytometry; D005559:Formamides / Q000008:administration & dosage*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D005559:Formamides; D016023:Integrins; D004317:Doxorubicin; D002945:Cisplatin; C002950:methylformamide