CYP2W1: Endogenous function and role in cancer therapy

Details

Serval ID
serval:BIB_7C4D4B146A3D
Type
Inproceedings: an article in a conference proceedings.
Collection
Publications
Institution
Title
CYP2W1: Endogenous function and role in cancer therapy
Title of the conference
Second ESPT Conference “Pharmacogenomics: From Cell to Clinic
Author(s)
Choong E., Guo J., Persson A., Virding S., Mkrtchian S., Ingelman-Sundberg M.
Publication state
Published
Issued date
28/09/2013
Language
english
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. We have recently shown CRC-specific expression of the orphan cytochrome P450 2W1 (CYP2W1) that belongs to a P450 monoxygenases family involved in detoxification of xenobiotics, drugs and also in the metabolism of certain endogenous compounds. CYP2W1 expression is associated with less survival rate in CRC stages II and III (1, 2). CYP2W1 was suggested as an attractive target for CRC therapy by exploiting its ability to activate certain prodrugs to cytotoxic metabolites. This hypothesis was successfully confirmed in our laboratory both in vitro and in vivo on a murine xenograft model (3). In this context, the exploration of the mechanisms that control the CYP2W1 expression is of paramount importance as it may substantially increase the number of patients who would benefit from such CRC-specific therapy, including firstly the induction of CYP2W1 (in case of low or absent expression), and secondly treatment with CYP2W1-specific prodrugs. The key for determining CYP2W1 regulation might be found by studying the developmental pattern of its expression. The cyp2w1 protein has been detected in rat fetal colon and the gene is subsequently silenced in adult age (4), the expression pattern is reminiscent of the expression of many oncofetal genes. In this report, we present data on the analysis of the expression of cyp2w1 in mice colorectal tissues oof different ages from fetus to adulthood. Moreover, we have examined whether the same principle of specific fetal colon expression applies also to humans by analyzing the CYP2W1 expression on the mRNA and protein levels in fetal human colon (obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, MD (USA)). In addition, we also present data on the CYP2W1 regulatory mechanisms, potential substrates, inductors and inhibitors investigated in the different cell lines expressing CYP2W1. In conclusion, we examined the mechanisms of regulation and induction of the CYP2W1 expression. The project could provide novel information of high relevance for future treatment of colon cancer. Note: This study was approved by the Ethical Committee at Karolinska Institutet, Stockholm (Sweden). Literature 1. D. Edler et al., Eur J Cancer (2009). 2. K. Stenstedt et al., Anticancer research (2012). 3. S. Travica et al., Clin Cancer Res (2013). 4. M. Karlgren et al., Biochemical and biophysical research communications (2006).
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31/10/2022 14:31
Last modification date
01/11/2022 6:44
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