Dimethyl fumarate (DMF) inhibits proliferation and migration and induce cell death in solid tumor cells

Introduction Recently, we have shown in mouse models that dimethyl fumarate (DMF) treatment led to reduced metastasis formation and induction of cell death in malignant cells e. g. T-cell lymphoma. Solid tumors including hepatocellular carcinoma a characterized by a rather high ability to form metastasis. Therefore, we analyzed the effects of DMF on solid tumors.

Methods Various human cancer cell lines were treated with DMF and cellular ATP content was measured using a luminescence-based assay. Scratch assays with different tumor cell lines were performed to investigate whether DMF affects migration. In addition, cell proliferation of was determined either by FACS analysis or a colorimetric based assays. Flow cytometry was applied to analyze cell death induction.

Results DMF application resulted in a dose-dependent depletion of up to 89 % of cellular ATP content depending on the cell line tested. Thus, we analyzed whether the decrease in ATP level induced cell death and/or inhibited proliferation and migration. In accordance to ATP-depletion the tumor cell lines showed a strongly diminished proliferation (up to 89%) and migration (up to 100% inhibition). Furthermore, DMF application resulted dependent on the dose and cell line in up to 46% cell death.

Conclusion We could show that DMF is capable to induce energy depletion resulting in a reduced migration and proliferation in various tumor cell lines. Furthermore, DMF was able to induce cell death. DMF is clinical approved and could be used as a basis to develop novel treatment options for treatment of metastasis formation.

Publikationsverlauf

Artikel online veröffentlicht:
26. Januar 2022