Literature DB >> 23454010

Differential effect of adenosine receptors on growth of human colon cancer HCT 116 and HT-29 cell lines.

Monika Sakowicz-Burkiewicz1, Agnieszka Kitowska, Marzena Grden, Izabela Maciejewska, Andrzej Szutowicz, Tadeusz Pawelczyk.   

Abstract

The study aimed to evaluate the impact of adenosine receptors (ARs) on human colon tumor cells (HCT 116, HT-29) growth and sensitivity to 5-Fluorouracil (5-FU) an anticancer chemotherapeutic drug. The exposure of cancer cells to a selective A(3)-AR agonist (IB-MECA) resulted in an increase in HT-29 cells number, whereas the number of HCT 116 cells decreased significantly. In the presence of IB-MECA (1 μM) the percentage of apoptotic HT-29 cells significantly decreased, whereas the number of apoptotic and necrotic HCT 116 cells increased by 3- and 2,5-fold, respectively. The application of a selective A(2A)-AR agonist resulted in the increased survival of HCT 116 cells, but not HT-29 cells. The blockade of A(2A)-AR with ZM 241385 (0.1 μM) significantly increased the cytotoxicity of 5-FU (1 μM) in HCT 116 cells but not in HT-29 cells. The suppression of A(3)-AR with MRS 1523 (1 μM) increased the sensitivity of HT-29 cells to 5-FU while response of HCT 116 cells to 5-FU decreased. The growth promoting effect of IB-MECA in HT-29 cells was associated with the decreased intracellular cAMP level, whereas IB-MECA growth inhibitory effect in HCT 116 cells was abolished by okadaic acid (2 nM) indicating the involvement of protein phosphatase PP2A.
Copyright © 2013 Elsevier Inc. All rights reserved.

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Year:  2013        PMID: 23454010     DOI: 10.1016/j.abb.2013.02.007

Source DB:  PubMed          Journal:  Arch Biochem Biophys        ISSN: 0003-9861            Impact factor:   4.013


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