Open AccessThe in vitro effects of CRE‐decoy oligonucleotides in combination with conventional chemotherapy in colorectal cancer cell lines
Author(s) -
Liu Wai M.,
Scott Katherine A.,
Shahin Sipra,
Propper David J.
Publication year - 2004
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.2004.04208.x
Subject(s) - cdk inhibitor , cyclin dependent kinase , decoy , cell growth , cancer research , colorectal cancer , transcription factor , biology , cell culture , cell cycle , microbiology and biotechnology , cell , cancer , gene , biochemistry , genetics , receptor
The cAMP response element consensus sequence directs the transcription of a wide range of genes. A 24‐mer single‐stranded cAMP response element decoy oligonucleotide (CDO) has been shown to compete with these sequences for binding transcription factors and therefore interferes with cAMP‐induced gene transcription. We have examined the effect of this CDO alone and in combination with a range of common chemotherapeutic agents in colorectal cancer cell lines. CDO had a potent anti‐proliferative effect in colorectal cell lines, yet, a similar enhancement of cell death was not observed. Simple drug–drug interaction studies showed that combining CDO with chemotherapy resulted in an enhancement of the antiproliferative effects. Furthermore, this cytostatic effect was protracted and associated with an increase in senescence‐associated β‐galactosidase activity at pH 6. There is a possible role for p21 waf1 in mediating this effect, as the enhancement of cell growth inhibition was not observed in cells lacking the ability to correctly upregulate this protein. Additionally, significant decreases in cyclin‐dependent kinase (CDK) 1 and CDK 4 function were seen in the responsive cells. These data provide a possible model of drug interaction in colorectal cell lines, which involves the complex interplay of the molecules regulating the cell cycle. Clinically, the cytostatic ability of CDO could improve and enhance the antiproliferative effects of conventional cytotoxic agents.