The PI3K/Akt pathway in colitis associated colon cancer and its chemoprevention with celecoxib, a Cox-2 selective inhibitor

Setia, Shruti; Nehru, Bimla; Sanyal, Sankar Nath

doi:10.1016/j.biopha.2014.07.006

Cited by 25 publications

(12 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, it has been also shown that infliximab, an anti-TNF-alpha antibody, could prevent CAC in DSS-induced colitis, an effect which was accompanied by the reduction of MMP-9 and MMP-11 levels [ 155 ]. Similar results were observed when omeprazole exerted a proapoptotic effect in a model of CAC and inhibited MMP-9 and -11 and MT1-MMP [ 156 ] and celecoxib reduced gelatinase colon levels in models of CAC [ 157 ].…”

Section: New Evidence For Functions Of Mmps In Ibdsupporting

confidence: 69%

Matrix Metalloproteinases in Inflammatory Bowel Disease: An Update

O'Sullivan

Gilmer

Medina

2015

Mediators of Inflammation

134

119

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) are known to be upregulated in inflammatory bowel disease (IBD) and other inflammatory conditions, but while their involvement is clear, their role in many settings has yet to be determined. Studies of the involvement of MMPs in IBD since 2006 have revealed an array of immune and stromal cells which release the proteases in response to inflammatory cytokines and growth factors. Through digestion of the extracellular matrix and cleavage of bioactive proteins, a huge diversity of roles have been revealed for the MMPs in IBD, where they have been shown to regulate epithelial barrier function, immune response, angiogenesis, fibrosis, and wound healing. For this reason, MMPs have been recognised as potential biomarkers for disease activity in IBD and inhibition remains a huge area of interest. This review describes new roles of MMPs in the pathophysiology of IBD and suggests future directions for the development of treatment strategies in this condition.

show abstract

Section: New Evidence For Functions Of Mmps In Ibdsupporting

confidence: 69%

Matrix Metalloproteinases in Inflammatory Bowel Disease: An Update

O'Sullivan

Gilmer

Medina

2015

Mediators of Inflammation

134

119

View full text Add to dashboard Cite

show abstract

“…Both pre‐clinical and clinical studies of osteoarthritis and rheumatoid arthritis have demonstrated the efficacy of celecoxib was superior to placebo treatment . Previous mechanism studies indicated that the anti‐inflammatory effect induced by celecoxib was attributed to suppression of AKT/mTOR and NF‐κB‐mediated inflammatory pathways . In addition, strong evidence also showed that celecoxib induced anti‐oxidative effects in multiple diseases characterized by downregulation of ROS production, and upregulation of antioxidant levels .…”

Section: Discussionmentioning

confidence: 99%

Celecoxib prevents pressure overload‐induced cardiac hypertrophy and dysfunction by inhibiting inflammation, apoptosis and oxidative stress

Zhang

Fan

Ying-xia

et al. 2015

J Cellular Molecular Medi

View full text Add to dashboard Cite

To explore the effects of celecoxib on pressure overload‐induced cardiac hypertrophy (CH), cardiac dysfunction and explore the possible protective mechanisms. We surgically created abdominal aortic constrictions (AAC) in rats to induce CH. Rats with CH symptoms at 4 weeks after surgery were treated with celecoxib [2 mg/100 g body‐weight(BW)] daily for either 2 or 4 weeks. Survival rate, blood pressure and cardiac function were evaluated after celecoxib treatment. Animals were killed, and cardiac tissue was examined for morphological changes, cardiomyocyte apoptosis, fibrosis, inflammation and oxidative stress. Four weeks after AAC, rats had significantly higher systolic, diastolic and mean blood pressure, greater heart weight and enlarged cardiomyocytes, which were associated with cardiac dysfunction. Thus, the CH model was successfully established. Two weeks later, animals had impaired cardiac function and histopathological abnormalities including enlarged cardiomyocytes and cardiac fibrosis, which were exacerbated 2 weeks later. However, these pathological changes were remarkably prevented by the treatment of celecoxib, independent of preventing hypertension. Mechanistic studies revealed that celecoxib‐induced cardiac protection against CH and cardiac dysfunction was due to inhibition of apoptosis via the murine double mimute 2/P53 pathway, inhibition of inflammation via the AKT/mTOR/NF‐κB pathway and inhibition of oxidative stress via increases in nuclear factor E2‐related factor‐2‐mediated gene expression of multiple antioxidants. Celecoxib suppresses pressure overload‐induced CH by reducing apoptosis, inflammation and oxidative stress.

show abstract

“…Although Figure 1 Previous studies with DMH-DSS combination claimed development of colonic tumors following treatment for 2 months (Setia, Nehru, & Sanyal, 2014). Although we did not encounter tumors, however, histological evaluation (Figure 2b,c GE, though safe for human consumption, is highly pungent, and some writhing was witnessed in animals following its oral administration.…”

Section: Resultsmentioning

confidence: 62%

“…Previous studies with DMH‐DSS combination claimed development of colonic tumors following treatment for 2 months (Setia, Nehru, & Sanyal, ). Although we did not encounter tumors, however, histological evaluation (Figure b,c) confirmed the development of precancerous lesions with presence of distorted atypical cells, abnormal crypts, and increased inflammatory burden in H&E and toluidine blue‐stained rat colon samples of PC group.…”

Section: Resultsmentioning

confidence: 95%

Coadministration of ginger extract–Lactobacillus acidophilus (cobiotic) reduces gut inflammation and oxidative stress via downregulation of COX‐2, i‐NOS, and c‐Myc

Deol

Khare

Bishnoi

et al. 2018

Phytotherapy Research

View full text Add to dashboard Cite

Aim of the study was to evaluate a combination of ginger extract (GE; antioxidant, anti-inflammatory) and Lactobacillus acidophilus (LAB; probiotic), in DMH-DSS-induced inflammation-driven colon cancer, in Wistar rats. Effect of varying GE concentration on growth of LAB was assessed in vitro. Colonic histology and permeability, oxidative stress, serum proinflammatory cytokines, expression of selected genes, gut bacteria, and SCFA determination of gut content was monitored after treatment with agents alone or in combination, postdisease induction. Significant increase in LAB CFU was observed following 48 and 96 hr of incubation with GE; 0.4% w/v GE showed the best results and was used in the cobiotic. Cobiotic administration significantly reversed the DMH-DSS-induced colonic histological alterations. Significant (p < .05) reduction in lipid peroxidation and increase in antioxidant levels (catalase and SOD) was observed in cobiotic group, whereas individual agents did not show any effect. Restoration of colonic permeability, decrease in serum inflammatory burden, and downregulation of COX-2, iNOS, and c-Myc expression on treatment with cobiotic was significantly (p < .05) better than individual agents. Neither LAB nor cobiotic administration produced any change in gut bacteria nor SCFA levels, probably due to loss of LAB viability under adverse gut conditions. Study concludes that presented cobiotic has a promising therapeutic potential, which can be improved by a smartly designed formulation.

show abstract

The PI3K/Akt pathway in colitis associated colon cancer and its chemoprevention with celecoxib, a Cox-2 selective inhibitor

Cited by 25 publications

References 32 publications

Matrix Metalloproteinases in Inflammatory Bowel Disease: An Update

Matrix Metalloproteinases in Inflammatory Bowel Disease: An Update

Celecoxib prevents pressure overload‐induced cardiac hypertrophy and dysfunction by inhibiting inflammation, apoptosis and oxidative stress

Coadministration of ginger extract–Lactobacillus acidophilus (cobiotic) reduces gut inflammation and oxidative stress via downregulation of COX‐2, i‐NOS, and c‐Myc

Contact Info

Product

Resources

About