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Chloride channels: Role in apoptosis, cell motility and chemotherapy resistance
Author(s) -
Hoffmann Else Kay,
Jacobsen Kari S,
Schwab Albrecht,
Sauter Daniel,
Lambert Ian H,
Poulsen Kristian A
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.913.15
Subject(s) - cisplatin , apoptosis , cancer research , multiple drug resistance , cell culture , motility , biology , cell , western blot , chemotherapy , programmed cell death , microbiology and biotechnology , chemistry , biochemistry , drug resistance , gene , genetics
Among the pathophysiological phenotypes defining malignant growth are cell migration and evasion of programmed cell death. The talk will discuss how Cl − channels affect these processes and how changes in the expression of Cl − channels are involved in chemotherapy resistance. We investigate the role of the TMEM16 Cl − channels in cell migration in Ehrlich Lettré Ascites (ELA) cells and find that TMEM16A and TMEM16F knock‐down affects the directional migration and the rate of cell migration, respectively. Moreover we have explored the apoptotic volume decrease (AVD) in wild type (wt) and Multidrug Resistant (MDR) Ehrlich Ascites Tumor Cells (EATC). Cisplatin (5 μM) leads to AVD and apoptosis in wt EATC but essentially not in MDR cells, and the maximal capacity of the volume activated Cl − current is concomitantly strongly repressed in MDR EATC. Application of the VRAC inhibitor NS3728 prevents cisplatin‐induced AVD in wt cells and abolishes the differences in AVD and caspase‐3 activation between wt and MDR EATC suggesting that impairment of AVD via down regulation of Cl − channels protects against apoptosis in MDR EATC1. Currently, using QPCR and western blot we compare the expression of Cl − channels in wt and MDR EATC as well as in four pancreatic cancer cell lines and a normal pancreatic cell line (HPDE). Supported by DFF, Denmark.