Evaluation of functional changes in akr overexpressing colorectal cell line sw480

Ermiş, Çağdaş
The Aldo-Keto Reductases (AKR) are nicotinamide adenine dinucleotide (NAD(P)H) dependent oxidoreductases that function in phase 1 metabolismbyreducingaldehydes and ketones into primary and secondary alcohols. Inthis protein superfamily, the expression of AKR1B1 and AKR1B10 enzymes have been linked by us and others to colorectal cancer (CRC). Over-activation of these enzymes in the presence of excess glucose can result in the activation of the polyol pathway, which causes oxidative stress and might contribute to the progression of cancer. Substrates of the AKR enzymes varyfrom sugars to various chemical carcinogens. Many studies suggest that chemotherapy drugs can also be metabolized by these enzymes, leading to drug resistance. On the other hand, a link between these enzymes and a mesenchymal phenotype has also been gaining attention. In this study, we aimed to investigate the effects of overexpression of two AKR enzymes, AKR1B1 and AKR1B10, on CRC cell line SW480, which does not have the endogenous expression of either gene. We observed that AKR1B1 overexpressing cells showed higher motility and weaker cell-cell adhesionbut no significant change in proliferation. These data are consistent with previous findings on a strong and significant positive correlation between the expression of AKR1B1 and several different mesenchymal markers. We also show for the first time that serum-starvedAKR1B1 expressing cells expressed higher protein levels of arate-limitingenzyme of the pentose phosphate pathway, most likely as a means to cope with the increasedoxidative stress in the starved cells. AKR1B10 overexpressing cells were significantly less motile, showed a slower cell cycle progression and a reduced clonogenic potential. Overall, our data corroborateprevious reports on the highly divergent effects of two very closely related enzymes in colorectal cancer.


Evaluation of functional changes in akr1b1 and akr1b10 overexpressing colorectal cancer cell lines
Güderer, İsmail; Banerjee, Sreeparna; Department of Biology (2021-2-15)
Aldo-keto reductases (AKRs) are nicotinamide adenine dinucleotide phosphate (NADPH)-dependent enzymes with diverse cellular metabolism functions. AKR1B1 and AKR1B10 are two of the most studied enzymes in the AKR family. AKR1B1 reduces excess glucose into sorbitol using reducing electrons from NADPH, and the hyperactivation of the AKR1B1 pathways is associated with oxidative stress and cell death. AKR1B10 is a poor reductant of glucose but is a vital enzyme that can metabolize retinol and many other drugs an...
Evaluation of an aldo-keto reductase gene signature with prognostic significance in colon cancer via activation of epithelial to mesenchymal transition and the p70S6K pathway
Canli, Secil Demirkol; Seza, Esin Gulce; Sheraj, Ilir; Gomceli, Ismail; Turhan, Nesrin; Carberry, Steven; Prehn, Jochen H. M.; GÜRE, ALİ OSMAY; Banerjee, Sreeparna (Oxford University Press (OUP), 2020-09-01)
AKR1B1 and AKR1B10, members of the aldo-keto reductase family of enzymes that participate in the polyol pathway of aldehyde metabolism, are aberrantly expressed in colon cancer. We previously showed that high expression of AKR1B1 (AKR1B1(HIGH)) was associated with enhanced motility, inflammation and poor clinical outcome in colon cancer patients. Using publicly available datasets and ex vivo gene expression analysis (n = 51, Ankara cohort), we have validated our previous in silico finding that AKR1B1(HIGH) ...
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Enzymatic metabolism of the 20C polyunsaturated fatty acid (PUFA) arachidonic acid (AA) occurs via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways, and leads to the production of various bioactive lipids termed eicosanoids. These eicosanoids have a variety of functions, including stimulation of homeostatic responses in the cardiovascular system, induction and resolution of inflammation, and modulation of immune responses against diseases associated with chronic inflammation, such as cancer. Because...
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Tranilast is an antiallergic drug that interferes with proliferation and migration of vascular smooth muscle cell induced by platelet-derived growth factor (PDGF) and transforming growth factor-beta 1 (TGF-beta 1). We investigated the local effect of tranilast on neointimal hyperplasia using tranilastcoated prosthetic grafts. The inner sides of the thin-walled polytetrafluoroethylene (PTFE) grafts were coated with chitosan and tranilast containing chitosan solution. Wistar albino rats (32) were used in the ...
Comparative analysis of product and by-product distributions in defined and complex media in serine alkaline protease production by recombinant Basillus subtilis
Oktar, Ceren; Çalık, Pınar; Department of Chemical Engineering (2003)
In this study, firstly the effects of aspartic acid group amino acids -which were reported to be the potential bottleneck in serine alkaline protease (SAP) synthesis- on SAP production were investigated by substituting at a concentration range of 0-15 mM by using recombinant Bacillus subtilis carrying pHV1434::subC gene. All aspartic acid group amino acids except threonine inhibited SAP activity when CAA= 2.5 mM. The highest SAP activities with asparagine, aspartic acid, lysine, threonine, isoleucine and me...
Citation Formats
Ç. Ermiş, “Evaluation of functional changes in akr overexpressing colorectal cell line sw480,” M.S. - Master of Science, Middle East Technical University, 2021.