title: The effects of 1,4-dimethylpyridine in metastatic prostate cancer in mice.
abstract: We previously showed that 1-methylnicotinamide (1-MNA) and its analog 1,4-dimethylpyridine (1,4-DMP) could inhibit the formation of lung metastases and enhance the efficacy of cyclophosphamide-based chemotherapy in the model of spontaneously metastasizing 4T1 mouse mammary gland tumors. In the present study, we aimed to investigate whether the previously observed activity of pyridine compounds pertains also to the prevention and the treatment of metastatic prostate tumors, in a combined chemotherapy with docetaxel.
  
  
  
  Cancer-preventing activity of 1,4-DMP was studied in the model of prostate tumors spontaneously arising in C57BL/6-Tg (TRAMP)8247Ng/J (TRAMP) mice. The efficacy of the combined chemotherapy, comprising simultaneous use of 1,4-DMP and docetaxel, was evaluated in the orthotopic mouse model of human PC-3M-luc2 prostate cancer. The toxicity of the applied treatment was also determined.
  
  
  
  The development of prostate tumors in TRAMP mice remained unaffected after administration of 1,4-DMP. Similarly, no effect of 1,4-DMP was found on the growth of orthotopically transplanted PC-3M-luc2 tumors. However, when 1,4-DMP was administered along with docetaxel, it enhanced the anticancer activity of the chemotherapy. As a result, in PC-3M-luc2-bearing mice statistically significant inhibition of the tumor growth and lower metastases incidence were observed. The decreased metastatic yield is probably related to the diminished platelet activity observed in mice treated with combined therapeutic regimen. Finally, the combined treatment exhibited lowered side effects accompanying docetaxel administration.
  
  
  
  Results presented herein confirm previously published data on the anticancer activity of pyridine compounds and demonstrate that 1,4-DMP may be beneficially implemented into chemotherapy utilizing various cytotoxic agents, directed against multiple metastatic tumor types.
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, Wroclaw, 53-114, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Denslow
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, Wroclaw, 53-114, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Switalska
authors.affiliation: Wroclaw University of Environmental and Life Sciences, Norwida 31, Wroclaw, 50-375, 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, Wroclaw, 53-114, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Maciejewska
authors.affiliation: Chair of Pharmacology, Jagiellonian University, Medical College, Grzegorzecka 16, Krakow, 31-531, Poland.|Jagiellonian Center for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, Krakow, 30-348, Poland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Chlopicki
authors.affiliation: Lodz University of Technology, Zeromskiego 116, Lodz, 90-924, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Marcinek
authors.affiliation: Lodz University of Technology, Zeromskiego 116, Lodz, 90-924, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Gebicki
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, Wroclaw, 53-114, Poland. wietrzyk@iitd.pan.wroc.pl.
authors.forename: Joanna
authors.identifier: 0000-0003-4980-6606
authors.initials: J
authors.lastname: Wietrzyk
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004195:Disease Models, Animal; D000077143:Docetaxel; D006801:Humans; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011725:Pyridines / Q000008:administration & dosage*; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D011725:Pyridines; D043823:Taxoids; D000077143:Docetaxel; D009536:Niacinamide; D003520:Cyclophosphamide; C023666:pyridine; C024058:N(1)-methylnicotinamide
keywords: 1,4-dimethylpyridine; 1-methylnicotinamide; Combined therapy; Docetaxel; Metastasis; Prevention; Prostate cancer