title: 1-methylnicotinamide and its structural analog 1,4-dimethylpyridine for the prevention of cancer metastasis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Blazejczyk
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Switalska
authors.affiliation: Chair of Pharmacology, Jagiellonian University, Medical College, Grzegórzecka 16, 31-531, Krakow, Poland.|Jagiellonian Center for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Chlopicki
authors.affiliation: Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Marcinek
authors.affiliation: Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Gebicki
authors.affiliation: Wroclaw University of Environmental and Life Sciences, Norwida 31, 50-375, Wroclaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Nowak
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Nasulewicz-Goldeman
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland. wietrzyk@iitd.pan.wroc.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D064200:Cdh1 Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D011464:Epoprostenol; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008175:Lung Neoplasms / Q000098:blood supply / Q000517:prevention & control* / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D015820:Cadherins; D064200:Cdh1 Proteins; C489083:Cdh2 protein, mouse; C577585:Fzr1 protein, mouse; D011726:Pyridinium Compounds; D009536:Niacinamide; D011464:Epoprostenol; C024058:N(1)-methylnicotinamide
keywords: 1,4-dimethylpyridinium chloride; 1-methylnicotinaimide chloride; Angiogenesis; Breast cancer; Combined therapy; Metastasis