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J Exp Clin Cancer Res. 2016 Jul 13;35(1):110. doi: 10.1186/s13046-016-0389-9.

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

Author information

1
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland.
2
Chair of Pharmacology, Jagiellonian University, Medical College, Grzegórzecka 16, 31-531, Krakow, Poland.
3
Jagiellonian Center for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland.
4
Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.
5
Wroclaw University of Environmental and Life Sciences, Norwida 31, 50-375, Wroclaw, Poland.
6
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland. wietrzyk@iitd.pan.wroc.pl.

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.

KEYWORDS:

1,4-dimethylpyridinium chloride; 1-methylnicotinaimide chloride; Angiogenesis; Breast cancer; Combined therapy; Metastasis

PMID:
27412454
PMCID:
PMC4944260
DOI:
10.1186/s13046-016-0389-9
[Indexed for MEDLINE]
Free PMC Article

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