1-methylnicotinamide and its structural analog 1, 4-dimethylpyridine for the prevention of cancer metastasis. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Blazejczyk, Agnieszka; Switalska, Marta; Chlopicki, Stefan; Marcinek, Andrzej; Gebicki, Jerzy; Nowak, Marcin; Nasulewicz-Goldeman, Anna; Wietrzyk, Joanna
• Is Part Of: Journal of experimental & clinical cancer research. Volume 35:Issue 1(2016)
• Page Start: 1
• Page End: 13
• Publication Date: 2016-12
• Subjects: 1-methylnicotinaimide chloride -- 1, 4-dimethylpyridinium chloride -- Metastasis -- Angiogenesis -- Combined therapy -- Breast cancer; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s13046-016-0389-9
• Languages: English
• ISSNs: 1756-9966

Abstract

Abstract 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.