Anti-tumor potential of nitroxyl derivative Pirolin in the DMBA-induced rat mammary carcinoma model: A comparison with quercetin.
BACKGROUND
Considering the role of oxidative stress in carcinogenesis, we investigated the effect of synthetic antioxidant Pirolin (3-carbamoyl-2,2,5,5-tetramethylpyrroline-1-oxyl) on breast cancer progression. Since the anticancer drugs may cause cardiotoxicity due to oxidative stress in the heart muscle, we also evaluated Pirolin performance in heart tissue and compared its effect with that of the natural dietary flavonoid quercetin.


METHODS
Sprague-Dawley rats were administered with 7,12-dimethylbenz(a)anthracene (DMBA) and then treated ip with an antioxidant (each at a dose of 10mg/kg b.w.) for 14 days. The histopathology of tumors, their size and multiplicity were assesed. The effect of antioxidants on heart tissue was evaluated by the oxidative stress markers and poly (ADP-ribose) polymerase 1 (PARP 1) cleavage.


RESULTS
The median number of tumors and their volume, at the end of the study, were considerably smaller in both antioxidant-treated groups. We found a better antioxidative performance of quercetin in the heart, since a restoration of the GSH pool and decreased amount of hydroperoxides were observed. Antioxidants did not prevent cardiomyocytes from apoptosis.


CONCLUSIONS
The attenuation of tumor progression by Pirolin was comparable with the action of quercetin. No negative changes were observed in the heart of animals after Pirolin treatment. Thus, its use in targeting deregulated redox pathways should be further studied.
Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland. Electronic address: s.tabaczar@gmail.com.
Sabina
S
Tabaczar
Nofer Institute of Occupational Medicine, Łódź, Poland.
Katarzyna
K
Domeradzka
Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.
Jan
J
Czepas
Nofer Institute of Occupational Medicine, Łódź, Poland.
Joanna
J
Piasecka-Zelga
Nofer Institute of Occupational Medicine, Łódź, Poland.
Jan
J
Stetkiewicz
Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.
Krzysztof
K
Gwoździński
Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.
Aneta
A
Koceva-Chyła
D000818:Animals; D000873:Anthracenes / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009589:Nitrogen Oxides / Q000627:therapeutic use*; D010880:Piperidines / Q000633:toxicity*; D011794:Quercetin / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
C556780:3-(2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino)-2-thioxoimidazolidin-4-one on 7,12-dimethylbenz(a)anthracene; C575622:3-carbamoyl-2,2,5,5-tetramethylpyrroline-1-oxyl; D000873:Anthracenes; D000970:Antineoplastic Agents; D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D010880:Piperidines; D011794:Quercetin; C039900:nitroxyl
Flavonoid; Mammary carcinoma; Nitroxide; Oxidative stress; Quercetin