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...

Full description

Saved in:
Bibliographic Details
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
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
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
Reviewed by: Harikumar K.B., Rajiv Gandhi Centre for Biotechnology, India; Fabrizio Martelli, Istituto Superiore di Sanità, Italy
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2018.00314