Skip to main content
Top
Published in: Inflammopharmacology 5/2016

01-10-2016 | Original Article

α-Chymotrypsin regulates free fatty acids and UCHL-1 to ameliorate N-methyl nitrosourea induced mammary gland carcinoma in albino wistar rats

Authors: Asha Rani, Subhadeep Roy, Manjari Singh, Uma Devi, Rajnish K. Yadav, Swetlana Gautam, Jitendra K. Rawat, Mohd. Nazam Ansari, Abdulaziz S. Saeedan, Anand Prakash, Gaurav Kaithwas

Published in: Inflammopharmacology | Issue 5/2016

Login to get access

Abstract

This study was undertaken to investigate the effect of α-chymotrypsin on methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. Animals were randomized into four groups (six animals in each). Group I (sham control 0.9 % normal saline p.o.); Group II (toxic control, MNU 47 mg/kg, i.v.); Group III (α-chymotrypsin, 5 mg/kg, p.o.); Group IV (α-chymotrypsin, 10 mg/kg p.o.). Toxicity was induced by single i.v. injection of MNU followed by α-chymotrypsin supplementation therapy for 100 days. MNU treatment was evident with increased alveolar bud count, differentiation score, upregulated inflammatory enzymes markers (COX, LOX and NO) antioxidative stress markers (TBARs, SOD, catalase and GSH).MNU associated toxicity was also ascertained by PGP 9.5 and NF-κB expression in the mammary gland tissue followed by FAME analysis for fatty acid profiling. α-chymotrypsin afforded significant protection against the deleterious effects of MNU.
Appendix
Available only for authorised users
Literature
go back to reference Merlino A, Krauss IR (2014) Structural and denaturation studies of two mutants of a cold adapted superoxide dismutase point to the importance of electrostatic interactions in protein stability. Biochim Biophys Acta (BBA) Proteins Proteom 1844(3):632–640CrossRef Merlino A, Krauss IR (2014) Structural and denaturation studies of two mutants of a cold adapted superoxide dismutase point to the importance of electrostatic interactions in protein stability. Biochim Biophys Acta (BBA) Proteins Proteom 1844(3):632–640CrossRef
go back to reference Agradi E, Libertini L et al (1976) Specific modification of fatty acid synthetase from lactating rat mammary gland by chymotrypsin and trypsin. Biochem biophys Res Comm 68(3):894–900CrossRefPubMed Agradi E, Libertini L et al (1976) Specific modification of fatty acid synthetase from lactating rat mammary gland by chymotrypsin and trypsin. Biochem biophys Res Comm 68(3):894–900CrossRefPubMed
go back to reference Ahmad Y, Sharma N (2009) An effective method for the analysis of human plasma proteome using two-dimensional gel electrophoresis. J Proteom Bioinform 2(12):495–499CrossRef Ahmad Y, Sharma N (2009) An effective method for the analysis of human plasma proteome using two-dimensional gel electrophoresis. J Proteom Bioinform 2(12):495–499CrossRef
go back to reference Altman J, Sudarshan K (1975) Postnatal development of locomotion in the laboratory rat. Anim Behav 23:896–920CrossRefPubMed Altman J, Sudarshan K (1975) Postnatal development of locomotion in the laboratory rat. Anim Behav 23:896–920CrossRefPubMed
go back to reference Brichory F, Beer D et al (2001) Proteomics-based identification of protein gene product 9.5 as a tumor antigen that induces a humoral immune response in lung cancer. Cancer Res 61(21):7908–7912PubMed Brichory F, Beer D et al (2001) Proteomics-based identification of protein gene product 9.5 as a tumor antigen that induces a humoral immune response in lung cancer. Cancer Res 61(21):7908–7912PubMed
go back to reference Carrillo C, Cavia M et al (2012) Antitumor effect of oleic acid; mechanisms of action: a review. Nutri Hosp 27(6):1860–1865 Carrillo C, Cavia M et al (2012) Antitumor effect of oleic acid; mechanisms of action: a review. Nutri Hosp 27(6):1860–1865
go back to reference Chajès V, Thiébaut AC et al (2008) Association between serum trans-monounsaturated fatty acids and breast cancer risk in the E3 N-EPIC Study. Am J Epidemiol 167(11):1312–1320CrossRefPubMedPubMedCentral Chajès V, Thiébaut AC et al (2008) Association between serum trans-monounsaturated fatty acids and breast cancer risk in the E3 N-EPIC Study. Am J Epidemiol 167(11):1312–1320CrossRefPubMedPubMedCentral
go back to reference De Assis S, Warri A et al (2010) Changes in mammary gland morphology and breast cancer risk in rats. J Vis Exp 44:e2260–e2260 De Assis S, Warri A et al (2010) Changes in mammary gland morphology and breast cancer risk in rats. J Vis Exp 44:e2260–e2260
go back to reference Ellies LG, Fishman M et al (2003) Mammary tumor latency is increased in mice lacking the inducible nitric oxide synthase. Int J Cancer 106(1):1–7CrossRefPubMed Ellies LG, Fishman M et al (2003) Mammary tumor latency is increased in mice lacking the inducible nitric oxide synthase. Int J Cancer 106(1):1–7CrossRefPubMed
go back to reference Ellman GL, Courtney KD et al (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7(2):88–95CrossRefPubMed Ellman GL, Courtney KD et al (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7(2):88–95CrossRefPubMed
go back to reference Esslimani-Sahla M, Thezenas S et al (2007) Increased expression of fatty acid synthase and progesterone receptor in early steps of human mammary carcinogenesis. Int J Cancer 120(2):224–229CrossRefPubMed Esslimani-Sahla M, Thezenas S et al (2007) Increased expression of fatty acid synthase and progesterone receptor in early steps of human mammary carcinogenesis. Int J Cancer 120(2):224–229CrossRefPubMed
go back to reference Fay MP, Freedman LS et al (1997) Effect of different types and amounts of fat on the development of mammary tumors in rodents: a review. Cancer Res 57(18):3979–3988PubMed Fay MP, Freedman LS et al (1997) Effect of different types and amounts of fat on the development of mammary tumors in rodents: a review. Cancer Res 57(18):3979–3988PubMed
go back to reference Gregory EH, Pfaff DW (1971) Development of olfactory-guided behavior in infant rats. Physiol Behav 6(5):573–576CrossRefPubMed Gregory EH, Pfaff DW (1971) Development of olfactory-guided behavior in infant rats. Physiol Behav 6(5):573–576CrossRefPubMed
go back to reference Groll M, Huber R (2004) “Inhibitors of the eukaryotic 20S proteasome core particle: a structural approach”. Biochim Biophys Acta (BBA) Mol Cell Res 1695(1):33–44CrossRef Groll M, Huber R (2004) “Inhibitors of the eukaryotic 20S proteasome core particle: a structural approach”. Biochim Biophys Acta (BBA) Mol Cell Res 1695(1):33–44CrossRef
go back to reference Hegde AN, Upadhya SC (2011) Role of ubiquitin–proteasome-mediated proteolysis in nervous system disease. Biochim Biophys Acta (BBA) Gene Regul Mech 1809(2):128–140CrossRef Hegde AN, Upadhya SC (2011) Role of ubiquitin–proteasome-mediated proteolysis in nervous system disease. Biochim Biophys Acta (BBA) Gene Regul Mech 1809(2):128–140CrossRef
go back to reference Hormones E, BCC Group (2013) Sex hormones and risk of breast cancer in premenopausal women: a collaborative reanalysis of individual participant data from seven prospective studies. Lancet Oncol 14(10):1009–1019CrossRef Hormones E, BCC Group (2013) Sex hormones and risk of breast cancer in premenopausal women: a collaborative reanalysis of individual participant data from seven prospective studies. Lancet Oncol 14(10):1009–1019CrossRef
go back to reference Kaaks R, Rinaldi S et al (2005) Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr Relat Cancer 12(4):1071–1082CrossRefPubMed Kaaks R, Rinaldi S et al (2005) Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr Relat Cancer 12(4):1071–1082CrossRefPubMed
go back to reference Kaithwas G, Mukherjee A et al (2011) Antiinflammatory, analgesic and antipyretic activities of Linum usitatissimum L. (flaxseed/linseed) fixed oil. Indian J Exp Biol 49(12):932–938PubMed Kaithwas G, Mukherjee A et al (2011) Antiinflammatory, analgesic and antipyretic activities of Linum usitatissimum L. (flaxseed/linseed) fixed oil. Indian J Exp Biol 49(12):932–938PubMed
go back to reference Kaithwas G, Majumdar DK (2012) In vitro antioxidant and in vivo antidiabetic, antihyperlipidemic activity of linseed oil against streptozotocin-induced toxicity in albino rats. Eur J Lipid Sci Technol 114(11):1237–1245CrossRef Kaithwas G, Majumdar DK (2012) In vitro antioxidant and in vivo antidiabetic, antihyperlipidemic activity of linseed oil against streptozotocin-induced toxicity in albino rats. Eur J Lipid Sci Technol 114(11):1237–1245CrossRef
go back to reference Key T, Appleby P et al (2011) Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies. Br J Cancer 105(5):709–722CrossRefPubMed Key T, Appleby P et al (2011) Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies. Br J Cancer 105(5):709–722CrossRefPubMed
go back to reference Klaunig JE, Kamendulis LM et al (2010) Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol 38(1):96–109CrossRefPubMed Klaunig JE, Kamendulis LM et al (2010) Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol 38(1):96–109CrossRefPubMed
go back to reference Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(5259):680–685CrossRefPubMed Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(5259):680–685CrossRefPubMed
go back to reference Loewen PC, Villanueva J et al (2015) Unprecedented access of phenolic substrates to the heme active site of a catalase: Substrate binding and peroxidase-like reactivity of Bacillus pumilus catalase monitored by X-ray crystallography and EPR spectroscopy. Proteins Struct Funct Bioinf 83(5):853–866CrossRef Loewen PC, Villanueva J et al (2015) Unprecedented access of phenolic substrates to the heme active site of a catalase: Substrate binding and peroxidase-like reactivity of Bacillus pumilus catalase monitored by X-ray crystallography and EPR spectroscopy. Proteins Struct Funct Bioinf 83(5):853–866CrossRef
go back to reference Loizou S, Lekakis I et al (2010) β-Sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells. Mol Nutr Food Res 54(4):551–558CrossRefPubMed Loizou S, Lekakis I et al (2010) β-Sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells. Mol Nutr Food Res 54(4):551–558CrossRefPubMed
go back to reference Lyytinen H, Pukkala E et al (2009) Breast cancer risk in postmenopausal women using estradiol–progestogen therapy. Obstet Gynecol 113(1):65–73CrossRefPubMed Lyytinen H, Pukkala E et al (2009) Breast cancer risk in postmenopausal women using estradiol–progestogen therapy. Obstet Gynecol 113(1):65–73CrossRefPubMed
go back to reference Mäkelä A, Nuorti JP et al (2002) Neurologic disorders after measles-mumps-rubella vaccination. Pediatrics 110(5):957–963CrossRefPubMed Mäkelä A, Nuorti JP et al (2002) Neurologic disorders after measles-mumps-rubella vaccination. Pediatrics 110(5):957–963CrossRefPubMed
go back to reference Marques AJ, Palanimurugan R et al (2009) Catalytic mechanism and assembly of the proteasome. Chem Rev 109(4):1509–1536CrossRefPubMed Marques AJ, Palanimurugan R et al (2009) Catalytic mechanism and assembly of the proteasome. Chem Rev 109(4):1509–1536CrossRefPubMed
go back to reference Massot O, Baskevitch PP et al (1985) Estradiol increases the production of α 1-antichymotrypsin in MCF 7 and T 47 D human breast cancer cell lines. Mol Cell Endocrinol 42(3):207–214CrossRefPubMed Massot O, Baskevitch PP et al (1985) Estradiol increases the production of α 1-antichymotrypsin in MCF 7 and T 47 D human breast cancer cell lines. Mol Cell Endocrinol 42(3):207–214CrossRefPubMed
go back to reference Matsuyama M, Yoshimura R (2008) “The target of arachidonic acid pathway is a new anticancer strategy for human prostate cancer”. Biol Target Ther 2(4):725CrossRef Matsuyama M, Yoshimura R (2008) “The target of arachidonic acid pathway is a new anticancer strategy for human prostate cancer”. Biol Target Ther 2(4):725CrossRef
go back to reference Muchamuel T, Basler M et al (2009) A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med 15(7):781–787CrossRefPubMed Muchamuel T, Basler M et al (2009) A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med 15(7):781–787CrossRefPubMed
go back to reference Raj P, Singh M et al (2014) Effect of enteral administration of α-linolenic acid and linoleic acid against methotrexate induced intestinal toxicity in albino rats. RSC Adv 4(104):60397–60403CrossRef Raj P, Singh M et al (2014) Effect of enteral administration of α-linolenic acid and linoleic acid against methotrexate induced intestinal toxicity in albino rats. RSC Adv 4(104):60397–60403CrossRef
go back to reference Romon R, Adriaenssens E et al (2010) Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways. Mol Cancer 9(1):1CrossRef Romon R, Adriaenssens E et al (2010) Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways. Mol Cancer 9(1):1CrossRef
go back to reference Sasaki S, Horacsek M et al (1993) An ecological study of the relationship between dietary fat intake and breast cancer mortality. Prev Med 22(2):187–202CrossRefPubMed Sasaki S, Horacsek M et al (1993) An ecological study of the relationship between dietary fat intake and breast cancer mortality. Prev Med 22(2):187–202CrossRefPubMed
go back to reference Schapiro S, Salas M et al (1970) Hormonal effects on ontogeny of swimming ability in the rat: assessment of central nervous system development. Science 168(3927):147–151CrossRefPubMed Schapiro S, Salas M et al (1970) Hormonal effects on ontogeny of swimming ability in the rat: assessment of central nervous system development. Science 168(3927):147–151CrossRefPubMed
go back to reference Schneider T, Przewłocki R (2005) Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism. Neuropsychopharmacology 30(1):80–89CrossRefPubMed Schneider T, Przewłocki R (2005) Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism. Neuropsychopharmacology 30(1):80–89CrossRefPubMed
go back to reference Tokumaru Y, Yamashita K et al (2004) Inverse correlation between cyclin A1 hypermethylation and p53 mutation in head and neck cancer identified by reversal of epigenetic silencing. Cancer Res 64(17):5982–5987CrossRefPubMed Tokumaru Y, Yamashita K et al (2004) Inverse correlation between cyclin A1 hypermethylation and p53 mutation in head and neck cancer identified by reversal of epigenetic silencing. Cancer Res 64(17):5982–5987CrossRefPubMed
go back to reference Towbin H, Staehelin T et al (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci 76(9):4350–4354CrossRefPubMedPubMedCentral Towbin H, Staehelin T et al (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci 76(9):4350–4354CrossRefPubMedPubMedCentral
go back to reference Vatten LJ, Bjerve KS et al (1993) Polyunsaturated fatty acids in serum phospholipids and risk of breast cancer: a case-control study from the Janus serum bank in Norway. Eur J Cancer 29(4):532–538CrossRef Vatten LJ, Bjerve KS et al (1993) Polyunsaturated fatty acids in serum phospholipids and risk of breast cancer: a case-control study from the Janus serum bank in Norway. Eur J Cancer 29(4):532–538CrossRef
go back to reference Visekruna A, Joeris T et al (2006) Proteasome-mediated degradation of IκBα and processing of p105 in Crohn disease and ulcerative colitis. J Clin Investig 116(12):3195–3203CrossRefPubMedPubMedCentral Visekruna A, Joeris T et al (2006) Proteasome-mediated degradation of IκBα and processing of p105 in Crohn disease and ulcerative colitis. J Clin Investig 116(12):3195–3203CrossRefPubMedPubMedCentral
go back to reference Weiming X, Liu LZ et al (2002) The role of nitric oxide in cancer. Cell Res 12(5):311–320 Weiming X, Liu LZ et al (2002) The role of nitric oxide in cancer. Cell Res 12(5):311–320
go back to reference Wilcox P (1970) [5] Chymotrypsinogens—chymotrypsins. Method Enzymol 19:64–108CrossRef Wilcox P (1970) [5] Chymotrypsinogens—chymotrypsins. Method Enzymol 19:64–108CrossRef
go back to reference Zaridze D, Chevchenko V et al (1990) Fatty acid composition of phospholipids in erythrocyte membranes and risk of breast cancer. Int J Cancer 45(5):807–810CrossRefPubMed Zaridze D, Chevchenko V et al (1990) Fatty acid composition of phospholipids in erythrocyte membranes and risk of breast cancer. Int J Cancer 45(5):807–810CrossRefPubMed
go back to reference Zhao Q, Yang Y et al (2014) The clinicopathological significance of neurogenesis in breast cancer. BMC Cancer 14(1):1CrossRef Zhao Q, Yang Y et al (2014) The clinicopathological significance of neurogenesis in breast cancer. BMC Cancer 14(1):1CrossRef
Metadata
Title
α-Chymotrypsin regulates free fatty acids and UCHL-1 to ameliorate N-methyl nitrosourea induced mammary gland carcinoma in albino wistar rats
Authors
Asha Rani
Subhadeep Roy
Manjari Singh
Uma Devi
Rajnish K. Yadav
Swetlana Gautam
Jitendra K. Rawat
Mohd. Nazam Ansari
Abdulaziz S. Saeedan
Anand Prakash
Gaurav Kaithwas
Publication date
01-10-2016
Publisher
Springer International Publishing
Published in
Inflammopharmacology / Issue 5/2016
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-016-0280-5

Other articles of this Issue 5/2016

Inflammopharmacology 5/2016 Go to the issue