title: Differential effect of adenosine receptors on growth of human colon cancer HCT 116 and HT-29 cell lines.
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.
authors: Department of Molecular Medicine, Medical University of Gdansk, 80-211 Gdansk, Poland.
authors: Monika
authors: M
authors: Sakowicz-Burkiewicz
authors: Agnieszka
authors: A
authors: Kitowska
authors: Marzena
authors: M
authors: Grden
authors: Izabela
authors: I
authors: Maciejewska
authors: Andrzej
authors: A
authors: Szutowicz
authors: Tadeusz
authors: T
authors: Pawelczyk
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D054648:Protein Phosphatase 2 / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D043684:Receptor, Adenosine A3 / Q000235:genetics / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054648:Protein Phosphatase 2; D000241:Adenosine; D005472:Fluorouracil