1-methylnicotinamide and its structural analog 1,4-dimethylpyridine for the prevention of cancer metastasis

Background: 1-methylnicotinamide (1-mna),an endogenous metabolite of nicotinamide,has recently gained interest due to its anti-inflammatory and anti-thrombotic activities linked to the cox-2/pgi2 pathway. given the previously reported anti-metastatic activity of prostacyclin (pgi2),we aimed to assess the effects of 1-mna and its structurally related analog,1,4-dimethylpyridine (1,4-dmp),in the prevention of cancer metastasis. methods: all the studies on the anti-tumor and anti-metastatic activity of 1-mna and 1,4-dmp were conducted using the model of murine mammary gland cancer (4t1) transplanted either orthotopically or intravenously into female balb/c mouse. additionally,the effect of the investigated molecules on cancer cell-induced angiogenesis was estimated using the matrigel plug assay utilizing 4t1 cells as a source of pro-angiogenic factors. results: neither 1-mna nor 1,4-dmp,when given in a monotherapy of metastatic cancer,influenced the growth of 4t1 primary tumors transplanted orthotopically; however,both compounds tended to inhibit 4t1 metastases formation in lungs of mice that were orthotopically or intravenously inoculated with 4t1 or 4t1-luc2-tdtomato cells,respectively. additionally,while 1-mna enhanced tumor vasculature formation and markedly increased pgi2 generation,1,4-dmp did not have such an effect. the anti-metastatic activity of 1-mna and 1,4-dmp was further confirmed when both agents were applied with a cytostatic drug in a combined treatment of 4t1 murine mammary gland cancer what resulted in up to 80 % diminution of lung metastases formation. conclusions: the results of the studies presented below indicate that 1-mna and its structural analog 1,4-dmp prevent metastasis and might be beneficially implemented into the treatment of metastatic breast cancer to ensure a comprehensive strategy of metastasis control. © 2016 the author(s).