Anti-tumor and differentiation-inducing activity of N,N-dimethylformamide (DMF) in head-and-neck cancer xenografts.

Abstract

The anti-tumor activity of the putative differentiation-inducing agent dimethylformamide (DMF) was assessed in 7 head-and-neck xenograft (HNX) lines transplanted into nude mice. The drug was administered intra-peritoneally at the maximum tolerated dose. A significant growth-inhibitory effect was observed in 3 out of 7 tumor lines tested. When compared with 5 conventional drugs active in patients with squamous-cell carcinoma of the head and neck (HNSCC), DMF was as effective as the most active drugs (cisplatin and bleomycin). The most sensitive xenograft line, the poorly differentiated tumor HNX-14C, was used to test the hypothesis that differentiation induction might play a role in the anti-tumor activity of DMF. Light microscopic examination did not show clear-cut alteration of differentiation characteristics such as keratin and keratin pearl formation. Furthermore, we used a monoclonal antibody to study the expression of cytokeratin 10 which is useful as a differentiation marker of human HNSCC tumors. Keratin 10, not present in HNX-14C tumors grown under control conditions, became expressed in some cells upon DMF treatment. Further evidence for a differentiation-inducing activity of DMF was found in electron-microscopic studies. In treated HNX-14C tumors, in addition to cells with normal ultrastructural features, better-differentiated cells were observed, as manifested by an increase in the number of tonofilaments and desmosomes. The results show that DMF has a potential value for the treatment of patients with head-and-neck cancer, and that differentiation induction might play a role in the anti-tumor action of the drug.

• Authors: G A van Dongen, B J Braakhuis, A Leyva, H R Hendriks, B B Kipp, M Bagnay, G B Snow
• Journal: International journal of cancer (Int J Cancer) Vol. 43 Issue 2 Pg. 285-92 (Feb 15 1989) ISSN: 0020-7136 [Print] United States
• PMID: 2465278 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Keratins
• Dimethylformamide

Topics

• Animals
• Carcinoma, Squamous Cell (drug therapy, pathology, ultrastructure)
• Cell Differentiation (drug effects)
• Dimethylformamide (therapeutic use)
• Drug Evaluation, Preclinical
• Female
• Head and Neck Neoplasms (drug therapy, pathology, ultrastructure)
• Humans
• Keratins (analysis)
• Mice
• Mice, Nude
• Microscopy, Electron
• Neoplasm Transplantation
• Tumor Cells, Cultured