Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer

Bladder cancer remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression. Omega-3 polyunsaturated fatty acids and atorvastatin proved anti-inflammatory effects through peroxisome proliferator-activated rec...

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Main Authors: Nahla E El-Ashmawy, Eman G Khedr, Hoda A El-Bahrawy, Samar M Al-Tantawy
Format: Article
Language:English
Published: SAGE Publishing 2017-02-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317692254
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author Nahla E El-Ashmawy
Eman G Khedr
Hoda A El-Bahrawy
Samar M Al-Tantawy
author_facet Nahla E El-Ashmawy
Eman G Khedr
Hoda A El-Bahrawy
Samar M Al-Tantawy
author_sort Nahla E El-Ashmawy
collection DOAJ
description Bladder cancer remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression. Omega-3 polyunsaturated fatty acids and atorvastatin proved anti-inflammatory effects through peroxisome proliferator-activated receptor gamma mechanism. However, their chemopreventive effect still remained to be examined and clarified. In this study, bladder cancer was induced in rats by the chemical carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. Omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid: 2:3 w/w; 1200 mg/kg) and/or atorvastatin (6 mg/kg) were given orally daily to rats for eight consecutive weeks concomitantly with N-butyl-N-(4-hydroxybutyl)nitrosamine and continued for further 4 weeks after cessation of N-butyl-N-(4-hydroxybutyl)nitrosamine administration. The histopathological examination of rat bladder revealed the presence of tumors and the absence of apoptotic bodies in sections from N-butyl-N-(4-hydroxybutyl)nitrosamine group, while tumors were absent and apoptotic bodies were clearly observed in sections from rat groups treated with omega-3 polyunsaturated fatty acids, atorvastatin, or both drugs. The study of the molecular mechanisms illustrated downregulation of COX-2 and P53 (mutant) genes and suppression of transforming growth factor beta-1 and the lipid peroxidation product malondialdehyde in serum of rats of the three treated groups. This chemopreventive effect was confirmed by and associated with lower level of bladder tumor antigen in urine. However, the combined treatment with both drugs exhibited the major protective effect and nearly corrected the dyslipidemia that has been induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. Collectively, omega-3 polyunsaturated fatty acids and atorvastatin, besides having anti-inflammatory properties, proved a chemopreventive effect against bladder cancer, which nominates them to be used as adjuvant therapy with other chemotherapeutics.
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spelling doaj-art-45aa5879b15341d69441a8b4d80cb1302025-08-20T03:58:21ZengSAGE PublishingTumor Biology1423-03802017-02-013910.1177/1010428317692254Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancerNahla E El-AshmawyEman G KhedrHoda A El-BahrawySamar M Al-TantawyBladder cancer remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression. Omega-3 polyunsaturated fatty acids and atorvastatin proved anti-inflammatory effects through peroxisome proliferator-activated receptor gamma mechanism. However, their chemopreventive effect still remained to be examined and clarified. In this study, bladder cancer was induced in rats by the chemical carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. Omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid: 2:3 w/w; 1200 mg/kg) and/or atorvastatin (6 mg/kg) were given orally daily to rats for eight consecutive weeks concomitantly with N-butyl-N-(4-hydroxybutyl)nitrosamine and continued for further 4 weeks after cessation of N-butyl-N-(4-hydroxybutyl)nitrosamine administration. The histopathological examination of rat bladder revealed the presence of tumors and the absence of apoptotic bodies in sections from N-butyl-N-(4-hydroxybutyl)nitrosamine group, while tumors were absent and apoptotic bodies were clearly observed in sections from rat groups treated with omega-3 polyunsaturated fatty acids, atorvastatin, or both drugs. The study of the molecular mechanisms illustrated downregulation of COX-2 and P53 (mutant) genes and suppression of transforming growth factor beta-1 and the lipid peroxidation product malondialdehyde in serum of rats of the three treated groups. This chemopreventive effect was confirmed by and associated with lower level of bladder tumor antigen in urine. However, the combined treatment with both drugs exhibited the major protective effect and nearly corrected the dyslipidemia that has been induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. Collectively, omega-3 polyunsaturated fatty acids and atorvastatin, besides having anti-inflammatory properties, proved a chemopreventive effect against bladder cancer, which nominates them to be used as adjuvant therapy with other chemotherapeutics.https://doi.org/10.1177/1010428317692254
spellingShingle Nahla E El-Ashmawy
Eman G Khedr
Hoda A El-Bahrawy
Samar M Al-Tantawy
Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer
Tumor Biology
title Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer
title_full Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer
title_fullStr Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer
title_full_unstemmed Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer
title_short Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer
title_sort chemopreventive effect of omega 3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer
url https://doi.org/10.1177/1010428317692254
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