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
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...
Main Authors: | , , , , |
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Format: | Article |
Language: | English |
Published: |
University of Belgrade, University of Novi Sad
2017-01-01
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Series: | Archives of Biological Sciences |
Subjects: | |
Online Access: | http://www.doiserbia.nb.rs/img/doi/0354-4664/2017/0354-46641600118A.pdf |
Summary: | 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 μg/100g) and p-coumaric acid (10.8 μg/100g). SF extract,
vanillic acid and p-coumaric acid exhibited high antiproliferative activities
in HT-29 cells, with IC50 values of 81.79μg/mL, 98.8 μM and 221.6 μM,
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. |
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ISSN: | 0354-4664 1821-4339 |