The results of the present study confirmed the constitutive expression of CYP2S1 and CYP2W1 in breast cancer cells, although their relatively low level of expression suggests that they may be less involved in the transformation of therapeutic agents in these types of tumors.
Indolines constitute high affinity exogenous compounds and specific chloromethylindolines have been shown to be activated by CYP2W1 into cytotoxic products in vitro and also in vivo, inhibiting the growth of human colon tumors in a mouse xenograft model.
The CRC specific localization of CYP2W1 and its effective prodrug activation makes it a very promising target for future development of cancer therapeutics.
However, significant CYP2W1 protein expression was found in only one tumor sample (a testosterone-producing adrenocortical carcinoma) and not in any normal tissue.
CYP2W1 has been proposed as an attractive target for colorectal cancer (CRC) therapy by exploiting its ability to activate duocarmycin prodrugs to cytotoxic metabolites.
The imatinib mediated induction of CYP2W1 suggests an adjuvant therapy to treatment with duocarmycins that thus would involve induction of tumorCYP2W1 levels followed by the CYP2W1 activated duocarmycin prodrugs.
These epidemiological data obtained from a large population of CRC patients and controls cannot confirm the previously suggested decreased risk for CRC among carriers of CYP2W1*2.
The analysis of colorectal normal and cancer tissues and CYP2W1 overexpressing human embryonic kidney (HEK) 293 cells showed that a fraction of CYP2W1 is modified by N-glycosylation.
The analysis of colorectal normal and cancer tissues and CYP2W1 overexpressing human embryonic kidney (HEK) 293 cells showed that a fraction of CYP2W1 is modified by N-glycosylation.
CYP2W1 is a novel enzyme shown to be selectively expressed in rat fetal colon and in human colon cancer and has previously been suggested as a potential drug target for cancer therapy.
The selective expression in some forms of cancers and the low expression in normal tissues render CYP2W1 as a possible drug target during cancer therapy.
The expression of CYP2W1 is colon tumor-specific and is associated with methylation status of the CYP2W1 gene, suggesting a potential causal link between the gene hypomethylation and its enhanced expression.
Methylation analysis of the CpG island in the exon 1-intron 1 junction of the CYP2W1 gene from both cell lines, tumors and normal tissues revealed that demethylated CpG dinucleotides appeared as a requirement for high CYP2W1 gene expression.