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.

Inhibition of Tumor Growth by Targeted Anti-EGFR/IGF-1R Nanobullets Depends on Efficient Blocking of Cell Survival Pathways

“…Although previous studies have reported the use of 14C xenograft models, ,− isolation and cross-sectioning of tumors after completion of the study revealed that especially large tumors were fluid filled rather than a solid mass (Figure S5 in the Supporting Information), possibly influencing tumor volume calculations based on external caliper measurements. It appears that subcutaneous implantation of 14C cells in mice results in the growth of cystic tumors (Prof. Dr. R. Brakenhoff, VU University Medical Center, Amsterdam, The Netherlands, personal communication).…”

Dual Effects of N,N-dimethylformamide on Cell Proliferation and Apoptosis in Breast Cancer

“… 4 , 5 DMF reduces the cholesterol level and increases the concentration of bile acid, indicating that there is a relationship between DMF and gut microbiotas. 6 Previous studies have also shown that DMF can promote apoptosis and inhibit tumor growth, such as head and neck cancer, 7 prostate cancer, 8 and ovarian cancer. 9 On the other hand, DMF enhances hepatocarcinogenicity in animal model.…”

Free Radical Intermediates in Sonodynamic Therapy

“…2), a widely used polar solvent, exhibits synergistic killing of HL‐60 human promyelocytic leukemia cells when combined with ultrasound 11. Anti‐tumor properties of DMF in the absence of ultrasound have been reported, 27 but its potential use for cancer therapy was limited due to the hepatotoxic effect of DMF. Jeffers et al demonstrated the cell killing by DMF and ultrasound at DMF concentrations (0.11 M), which by themselves were non‐toxic, thus improving the prospects for therapeutic application of DMF for locally intense chemotherapy 11.…”