DuCLOX-2/5 Inhibition Attenuates Inflammatory Response and Induces Mitochondrial Apoptosis for Mammary Gland Chemoprevention

The present study is a pursuit to define implications of dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention. The monotherapy and combination therapy of zaltoprofen (COX-2 inhibitor) and zileuton (5-LOX inhibi...

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Published inFrontiers in pharmacology Vol. 9; p. 314
Main Authors Gautam, Swetlana, Rawat, Atul K., Sammi, Shreesh R., Roy, Subhadeep, Singh, Manjari, Devi, Uma, Yadav, Rajnish K., Singh, Lakhveer, Rawat, Jitendra K., Ansari, Mohd N., Saeedan, Abdulaziz S., Kumar, Dinesh, Pandey, Rakesh, Kaithwas, Gaurav
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 06.04.2018
Subjects
angiogenesis
apoptosis
cyclooxygenase
DuCLOX-2/5 inhibition
lipoxygenase
NMR
Pharmacology
lipoxygenase
NMR
DuCLOX-2/5 inhibition
angiogenesis
apoptosis
cyclooxygenase
Zaltoprofen
Zileuton
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Abstract The present study is a pursuit to define implications of dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention. The monotherapy and combination therapy of zaltoprofen (COX-2 inhibitor) and zileuton (5-LOX inhibitor) were validated for their effect against methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. The combination therapy demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count and restoration of the histopathological architecture when compared to toxic control. DuCLOX-2/5 inhibition also upregulated levels of caspase-3 and caspase-8, and restored oxidative stress markers (GSH, TBARs, protein carbonyl, SOD and catalase). The immunoblotting and qRT-PCR studies revealed the participation of the mitochondrial mediated death apoptosis pathway along with favorable regulation of COX-2, 5-LOX. Aforementioned combination restored the metabolic changes to normal when scrutinized through H NMR studies. Henceforth, the DuCLOX-2/5 inhibition was recorded to import significant anticancer effects in comparison to either of the individual treatments.
AbstractList The present study is a pursuit to define implications of dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention. The monotherapy and combination therapy of zaltoprofen (COX-2 inhibitor) and zileuton (5-LOX inhibitor) were validated for their effect against methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. The combination therapy demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count and restoration of the histopathological architecture when compared to toxic control. DuCLOX-2/5 inhibition also upregulated levels of caspase-3 and caspase-8, and restored oxidative stress markers (GSH, TBARs, protein carbonyl, SOD and catalase). The immunoblotting and qRT-PCR studies revealed the participation of the mitochondrial mediated death apoptosis pathway along with favorable regulation of COX-2, 5-LOX. Aforementioned combination restored the metabolic changes to normal when scrutinized through 1 H NMR studies. Henceforth, the DuCLOX-2/5 inhibition was recorded to import significant anticancer effects in comparison to either of the individual treatments.
The present study is a pursuit to define implications of dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention. The monotherapy and combination therapy of zaltoprofen (COX-2 inhibitor) and zileuton (5-LOX inhibitor) were validated for their effect against methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. The combination therapy demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count and restoration of the histopathological architecture when compared to toxic control. DuCLOX-2/5 inhibition also upregulated levels of caspase-3 and caspase-8, and restored oxidative stress markers (GSH, TBARs, protein carbonyl, SOD and catalase). The immunoblotting and qRT-PCR studies revealed the participation of the mitochondrial mediated death apoptosis pathway along with favorable regulation of COX-2, 5-LOX. Aforementioned combination restored the metabolic changes to normal when scrutinized through 1H NMR studies. Henceforth, the DuCLOX-2/5 inhibition was recorded to import significant anticancer effects in comparison to either of the individual treatments.
The present study is a pursuit to define implications of dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention. The monotherapy and combination therapy of zaltoprofen (COX-2 inhibitor) and zileuton (5-LOX inhibitor) were validated for their effect against methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. The combination therapy demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count and restoration of the histopathological architecture when compared to toxic control. DuCLOX-2/5 inhibition also upregulated levels of caspase-3 and caspase-8, and restored oxidative stress markers (GSH, TBARs, protein carbonyl, SOD and catalase). The immunoblotting and qRT-PCR studies revealed the participation of the mitochondrial mediated death apoptosis pathway along with favorable regulation of COX-2, 5-LOX. Aforementioned combination restored the metabolic changes to normal when scrutinized through H NMR studies. Henceforth, the DuCLOX-2/5 inhibition was recorded to import significant anticancer effects in comparison to either of the individual treatments.
The present study is a pursuit to define implications of dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention. The monotherapy and combination therapy of zaltoprofen (COX-2 inhibitor) and zileuton (5-LOX inhibitor) were validated for their effect against methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. The combination therapy demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count and restoration of the histopathological architecture when compared to toxic control. DuCLOX-2/5 inhibition also upregulated levels of caspase-3 and caspase-8, and restored oxidative stress markers (GSH, TBARs, protein carbonyl, SOD and catalase). The immunoblotting and qRT-PCR studies revealed the participation of the mitochondrial mediated death apoptosis pathway along with favorable regulation of COX-2, 5-LOX. Aforementioned combination restored the metabolic changes to normal when scrutinized through 1H NMR studies. Henceforth, the DuCLOX-2/5 inhibition was recorded to import significant anticancer effects in comparison to either of the individual treatments.The present study is a pursuit to define implications of dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention. The monotherapy and combination therapy of zaltoprofen (COX-2 inhibitor) and zileuton (5-LOX inhibitor) were validated for their effect against methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. The combination therapy demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count and restoration of the histopathological architecture when compared to toxic control. DuCLOX-2/5 inhibition also upregulated levels of caspase-3 and caspase-8, and restored oxidative stress markers (GSH, TBARs, protein carbonyl, SOD and catalase). The immunoblotting and qRT-PCR studies revealed the participation of the mitochondrial mediated death apoptosis pathway along with favorable regulation of COX-2, 5-LOX. Aforementioned combination restored the metabolic changes to normal when scrutinized through 1H NMR studies. Henceforth, the DuCLOX-2/5 inhibition was recorded to import significant anticancer effects in comparison to either of the individual treatments.
Author Ansari, Mohd N.
Rawat, Jitendra K.
Devi, Uma
Saeedan, Abdulaziz S.
Pandey, Rakesh
Rawat, Atul K.
Singh, Lakhveer
Kaithwas, Gaurav
Gautam, Swetlana
Singh, Manjari
Yadav, Rajnish K.
Kumar, Dinesh
Sammi, Shreesh R.
Roy, Subhadeep
AuthorAffiliation 2 Center for Biomedical Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences Campus , Lucknow , India
4 Department of Pharmaceutical Sciences, Faculty of Health and Medical Sciences, Sam Higginbottom Institute of Agricultural Sciences and Technology , Allahabad , India
1 Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University) , Lucknow , India
5 Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University , Al-Kharj , Saudi Arabia
3 Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants , Lucknow , India
AuthorAffiliation_xml – name: 3 Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants , Lucknow , India
– name: 2 Center for Biomedical Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences Campus , Lucknow , India
– name: 4 Department of Pharmaceutical Sciences, Faculty of Health and Medical Sciences, Sam Higginbottom Institute of Agricultural Sciences and Technology , Allahabad , India
– name: 1 Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University) , Lucknow , India
– name: 5 Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University , Al-Kharj , Saudi Arabia
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Copyright Copyright © 2018 Gautam, Rawat, Sammi, Roy, Singh, Devi, Yadav, Singh, Rawat, Ansari, Saeedan, Kumar, Pandey and Kaithwas. 2018 Gautam, Rawat, Sammi, Roy, Singh, Devi, Yadav, Singh, Rawat, Ansari, Saeedan, Kumar, Pandey and Kaithwas
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Keywords lipoxygenase
NMR
DuCLOX-2/5 inhibition
angiogenesis
apoptosis
cyclooxygenase
Zaltoprofen
Zileuton
Language English
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Edited by: Anna Rita Migliaccio, Icahn School of Medicine at Mount Sinai, United States
This article was submitted to Cancer Molecular Targets and Therapeutics, a section of the journal Frontiers in Pharmacology
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Snippet The present study is a pursuit to define implications of dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) (DuCLOX-2/5) inhibition on various aspects of...
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StartPage 314
SubjectTerms angiogenesis
apoptosis
cyclooxygenase
DuCLOX-2/5 inhibition
lipoxygenase
NMR
Pharmacology
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Title DuCLOX-2/5 Inhibition Attenuates Inflammatory Response and Induces Mitochondrial Apoptosis for Mammary Gland Chemoprevention
URI https://www.ncbi.nlm.nih.gov/pubmed/29681851
https://www.proquest.com/docview/2029631216
https://pubmed.ncbi.nlm.nih.gov/PMC5897656
https://doaj.org/article/497bb025d28f42be86a2f0a46e27948c
Volume 9
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