Modulation of mRNA expression and activities of xenobiotic metabolizing enzymes, CYP1A1, CYP1A2, CYP2E1, GPx and GSTP1 by the Salicornia freitagii extract in HT-29 human colon cancer cells

İrtem Kartal, Deniz
Güray, Nülüfer Tülün
Phase I-II detoxification and antioxidant enzymes are responsible for the detoxification and elimination of activated carcinogens, acting as important biomarkers for chemoprevention. Among them, cytochrome P450s plays a prominent role in the metabolic activation of xenobiotics. The herb Salicornia freitagii (SF) (Amaranthaceae) is known for its anticancer, antioxidant, antidiabetic and antiinflammatory activities. In this study, we determined the bioactive phenolics in the SF methanol extract and investigated its antiproliferative potential in HT-29 human colon cancer cells. We also investigated the modulation of some phase I and II enzyme (CYP 1A1, 1A2, 2E1, GSTP1 and GPx) mRNA expression and enzymatic activities by the SF extract and its major bioactive phenolic compounds. LC/MS-MS analysis showed that the main phenolic compounds of the methanolic SF extract are vanillic acid (48 mu g/100g) and p-coumaric acid (10.8 mu g/100g). SF extract, vanillic acid and p-coumaric acid exhibited high antiproliferative activities in HT-29 cells, with IC50 values of 81.79 mu g/mL, 98.8 mu M and 221.6 mu M, respectively. The mRNA expression levels of CYP1A2 and CYP2E1 were decreased, while those of GSTP1 and GPx in HT-29 cells were increased after application of either the SF extract or vanillic acid. The SF extract by itself also increased the activities of GPx and GSTP1 enzymes 1.68- and 1.49-fold, respectively. Our data indicate that the SF extract and its major bioactive compound, vanillic acid, could exert a modulatory effect on the expression of enzymes that are involved in xenobiotic activation and detoxification pathways in the gastrointestinal tract. For this reason, SF can be considered as a natural source of chemopreventive agents.


Induction of Partial EMT with Nutrient Restriction and Lysosomal Alkalinization in Caco-2 Colorectal Cancer Cells
Hüsnügil, Hepşen Hazal; Banerjee, Sreeparna; Department of Biology (2022-8)
Limited availability of nutrients to cancer cells can result in metabolic rewiring, manifesting in the activation of processes such as autophagy for survival. Our study shows for the first time that Caco-2 cells incubated in a nutrient-restriction (NR) medium of low glucose, glutamine and serum for 48h were viable but less proliferative, demonstrated robust autophagy induction and lower sensitivity to 5- Fluorouracil. However, the cargo protein p62 was not degraded efficiently, suggesting a slower autop...
Synthesis of poly (dl-lactic-co-glycolic acid) coated magnetic nanoparticles for anti-cancer drug delivery
Tansık, Gülistan; Gündüz, Ufuk; Department of Biology (2012)
One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an extern...
KARAKURT, SERDAR; Adalı, Orhan (2011-01-01)
Glutathione S-transferase and NAD(P)H: quinone oxidoreductase 1 enzymes have important roles in detoxification and also activation of a wide variety of chemicals. Moreover, resistance of tumor cells against chemotherapeutic agents has been implicated in GST activities. The aim of this study was to investigate the effect of polyphenolic compound tannic acid on rabbit liver and kidney glutathione S-transferase and NAD(P)H: quinone oxidoreductase 1 enzyme activities. Tannic acid was found to be a potent inhibi...
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) ...
The Effect of 15-lipoxygenase-1 (15-LOX-1) on angiogenesis in colorectal and prostate cancer
Çolakoğlu, Melis; Banerjee, Sreeparna; Department of Biology (2017)
15-lipoxygenase-1 (15-LOX-1) is one of the lipoxygenases (LOX) that are important for the generation of inflammatory bioactive lipids, which then result in the initiation and resolution of inflammation. The enzyme mainly metabolizes the omega-6 fatty acid, linoleic acid, to 13-(S)-HODE. In colorectal carcinoma, the tumor suppressive role of 15-LOX-1 is highlighted with decreased proliferation, induction of apoptosis, reduced motility and invasion. Oppositely, the expression of 15-LOX-1 was reported to have ...
Citation Formats
A. ALTAY, D. İrtem Kartal, G. SADİ, N. T. Güray, and A. E. YAPRAK, “Modulation of mRNA expression and activities of xenobiotic metabolizing enzymes, CYP1A1, CYP1A2, CYP2E1, GPx and GSTP1 by the Salicornia freitagii extract in HT-29 human colon cancer cells,” ARCHIVES OF BIOLOGICAL SCIENCES, pp. 439–448, 2017, Accessed: 00, 2020. [Online]. Available: