Please use this identifier to cite or link to this item:
Title: Aquaporin 3 (AQP3) participates in the cytotoxic response to nucleoside-derived drugs
Author: Trigueros Motos, Laia
Pérez Torras, Sandra
Casado, Javier (Casado Merediz)
Molina Arcas, Míriam
Pastor Anglada, Marçal
Keywords: Farmacogenètica
Medicaments antineoplàstics
Antineoplastic agents
Issue Date: 14-Jan-2013
Publisher: BioMed Central Ltd
Abstract: Background: Nucleoside analogs used in the chemotherapy of solid tumors, such as the capecitabine catabolite 50-deoxy-5-fluorouridine (50-DFUR) trigger a transcriptomic response that involves the aquaglyceroporin aquaporin 3 along with other p53-dependent genes. Here, we examined whether up-regulation of aquaporin 3 (AQP3) mRNA in cancer cells treated with 50-DFUR represents a collateral transcriptomic effect of the drug, or conversely, AQP3 participates in the activity of genotoxic agents. Methods: The role of AQP3 in cell volume increase, cytotoxicity and cell cycle arrest was analyzed using loss-of-function approaches. Results: 50-DFUR and gemcitabine, but not cisplatin, stimulated AQP3 expression and cell volume, which was partially and significantly blocked by knockdown of AQP3. Moreover, AQP3 siRNA significantly blocked other effects of nucleoside analogs, including G1/S cell cycle arrest, p21 and FAS up-regulation, and cell growth inhibition. Short incubations with 5-fluorouracil (5-FU) also induced AQP3 expression and increased cell volume, and the inhibition of AQP3 expression significantly blocked growth inhibition triggered by this drug. To further establish whether AQP3 induction is related to cell cycle arrest and apoptosis, cells were exposed to long incubations with escalating doses of 5-FU. AQP3 was highly up-regulated at doses associated with cell cycle arrest, whereas at doses promoting apoptosis induction of AQP3 mRNA expression was reduced. Conclusions: Based on the results, we propose that the aquaglyceroporin AQP3 is required for cytotoxic activity of 5’-DFUR and gemcitabine in the breast cancer cell line MCF7 and the colon adenocarcinoma cell line HT29, and is implicated in cell volume increase and cell cycle arrest.
Note: Reproducció del document publicat a:
It is part of: BMC Cancer 2012, 12:434
Related resource:
ISSN: 1471-2407
Appears in Collections:Articles publicats en revistes (Institut de Biomedicina (IBUB))
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

Files in This Item:
File Description SizeFormat 
1471-2407-12-434.pdf1.09 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons