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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

The effects of 1,4-dimethylpyridine in metastatic prostate cancer in mice

Authors: Agnieszka Denslow, Marta Switalska, Marcin Nowak, Magdalena Maciejewska, Stefan Chlopicki, Andrzej Marcinek, Jerzy Gebicki, Joanna Wietrzyk

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
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Metadata
Title
The effects of 1,4-dimethylpyridine in metastatic prostate cancer in mice
Authors
Agnieszka Denslow
Marta Switalska
Marcin Nowak
Magdalena Maciejewska
Stefan Chlopicki
Andrzej Marcinek
Jerzy Gebicki
Joanna Wietrzyk
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3161-4

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