15-lipoxygenase-1 exerts its tumor suppressive role by inhibiting nuclear factor-kappa B via activation of PPAR gamma.

Date

2011-09-01

Author

Cimen, I
Astarci, E
Banerjee, Sreeparna

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

209
views

0
downloads

15-Lipoxygenase-1 (15-LOX-1) is an enzyme of the inflammatory eicosanoid pathway whose expression is known to be lost in colorectal cancer (CRC). We have previously shown that reintroduction of the gene in CRC cell lines slows proliferation and induces apoptosis (Cimen et al. [2009] Cancer Sci 100: 2283-2291). We have hypothesized that 15-LOX-1 may be anti-tumorigenic by the inhibition of the antiapoptotic inflammatory transcription factor nuclear factor kappa B. We show here that ectopic expression of 15-LOX-1 gene in HCT-116 and HT-29 CRC cell lines inhibited the degradation of inhibitor of kappa B (I kappa B alpha), decreased nuclear translocation of p65 and p50, decreased DNA binding in the nucleus and decreased transcriptional activity of Nuclear factor kappa B (NF-kappa B). As the 15-LOX-1 enzymatic product 13(S)-HODE is known to be a peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, and NF-kappa B can be inhibited by PPAR gamma, we examined whether activation of PPAR gamma was necessary for the abrogation of NF-kappa B activity. Our data show that the inhibition of both early and late stages of NF-kappa B activation could rescued by the PPARg antagonist GW9662 indicating that the inhibition was most likely mediated via PPAR gamma.

Subject Keywords

Cell Biology, Biochemistry, Molecular Biology

URI

https://hdl.handle.net/11511/37559

Journal

Journal of cellular biochemistry

DOI

https://doi.org/10.1002/jcb.23174

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

The NF-kappa B target genes ICAM-1 and VCAM-1 are differentially regulated during spontaneous differentiation of Caco-2 cells Astarci, Erhan; Sade, Asli; Cimen, Ismail; SAVAŞ, BERNA; Banerjee, Sreeparna (Wiley, 2012-08-01) Intestinal epithelial differentiation entails the formation of highly specialized cells with specific absorptive, secretory, digestive and immune functions. Cellcell and cellmicroenvironment interactions appear to be crucial in determining the outcome of the differentiation process. Using the Caco-2 cell line, which undergoes spontaneous re-differentiation when grown past confluency, we observed a loss of VCAM-1 (vascular cell adhesion molecule 1) mRNA expression, while ICAM-1 (intercellular cell adhesion m...
Drug repositioning as an effective therapy for protease-activated receptor 2 inhibition Saqib, Uzma; Savai, Rajkumar; Liu, DongFang; Banerjee, Sreeparna; Baig, Mirza S. (Wiley, 2019-02-01) Proteinase-activated receptor 2 (PAR-2) is a G protein-coupled receptor activated by both trypsin and a specific agonist peptide, SLIGKV-NH2. It has been linked to various pathologies, including pain and inflammation. Several peptide and peptidomimetic agonizts for PAR-2 have been developed exhibiting high potency and efficacy. However, the number of PAR-2 antagonists is smaller. We screened the Food and Drug Administration library of approved compounds to retrieve novel antagonists for repositioning in the...
Butyrate mediated regulation of RNA binding proteins in the post-transcriptional regulation of inflammatory gene expression Torun, Aydan; Enayat, Shabnam; Sheraj, Ilir; Tuncer, Sinem; Ulgen, Dogukan Hazar; Banerjee, Sreeparna (Elsevier BV, 2019-12-01) Short chain fatty acids (SCFAs) are produced by commensal bacteria in the gut and are known to reduce inflammation through transcriptional inhibition of cytokines and inflammatory proteins such as cyclooxygenase-2 (COX-2). Butyrate is a SCFA that was reported to alter the mRNA stability of inflammatory genes by increasiing the expression of the RNA binding protein (RBP) Tristetraprolin (TTP). We have hypothesized that butyrate may regulate gene expression post-transcriptionally through global effects on the...
NOS1-derived nitric oxide facilitates macrophage uptake of low-density lipoprotein. Roy, A; Banerjee, Sreeparna; Saqib, U; Baig, MS (Wiley, 2019-02-25) Foam cell formation is a hallmark event during atherosclerosis. The current paradigm is that lipid uptake by a scavenger receptor in macrophages initiates necrosis core formation that characterizes atherosclerosis. We report that NOS1‐derived nitric oxide (NO) facilitates low‐density lipoprotein (LDL) uptake by macrophages independent of the inflammatory response. LDL uptake could be dramatically suppressed by NOS1 specific inhibitor 1‐(2‐trifluoromethylphenyl) imidazole (TRIM). Importantly, the notion that...
Emerging cellular functions of the lipid metabolizing enzyme 15-Lipoxygenase-1 Colakoglu, Melis; Tuncer, Sinem; Banerjee, Sreeparna (Wiley, 2018-10-01) The oxygenation of polyunsaturated fatty acids such as arachidonic and linoleic acid through lipoxygenases (LOXs) and cyclooxygenases (COXs) leads to the production of bioactive lipids that are important both in the induction of acute inflammation and its resolution. Amongst the several isoforms of LOX that are expressed in mammals, 15-LOX-1 was shown to be important both in the context of inflammation, being expressed in cells of the immune system, and in epithelial cells where the enzyme has been shown to...

Citation Formats

I. Cimen, E. Astarci, and S. Banerjee, “15-lipoxygenase-1 exerts its tumor suppressive role by inhibiting nuclear factor-kappa B via activation of PPAR gamma.,” Journal of cellular biochemistry, pp. 2490–501, 2011, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/37559.