Swelling-activated taurine and K+ transport in human cervical cancer cells: association with cell cycle progression.
The aim of this study was to investigate swelling-activated taurine and K+ transport in human cervical cancer cells under various culture conditions, testing the hypothesis that the progression of cell cycle was accompanied by differential activities of swelling-activated transport pathways. Aphidicolin, an inhibitor of deoxyribonucleic acid (DNA) synthesis, was used to synchronize the cell cycle. The distribution of cell cycle stage was determined by fluorescence-activated cell sorting (FACS). Hypotonicity activated taurine efflux, which was sensitive to tamoxifen and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). Cell swelling also induced both Cl- -dependent and -independent K+ (86Rb+) efflux, presumably mediated by KCl cotransport (KCC) and Ca2+ -activated K+ channels, respectively. Cell cycle arrest in G0/G1 was accompanied by a remarkable decrease in the rate constant for swelling-activated taurine efflux, from 0.20+/-0.007 to 0.026+/-0.002 min(-1) (n=6). The activity of swelling-activated taurine efflux recovered progressively on re-entry into the cell cycle. After removal of aphidicolin and culture with 10% fetal calf serum for 10 h, the rate constant increased significantly from 0.026+/-0.002 to 0.093+/-0.002 min(-1) (n=6). After 24 h release from aphidicolin, the efflux rate constant had increased further to 0.195+/-0.006 min(-1) (n=6), a value not significantly different from that in normally proliferating cells. The differential activities of swelling-activated taurine transport matched well with our previous study showing a volume-sensitive anion channel associated with cell cycle progression. In contrast to the differential activities of swelling-activated taurine transport, swelling-activated K+ (86Rb+) transport was independent of the progression of cell cycle. Most importantly, pharmacological blockade of swelling-activated taurine efflux by tamoxifen or NPPB caused proliferating cervical cancer cells to arrest in G0/G1, suggesting that the activity of this efflux was associated with G1/S checkpoint progression. This study provides new and important information on the functional significance of swelling-activated transport system in the regulation of cell cycle clock of human cervical cancer cells.
Shen
M R
MR
University Laboratory of Physiology, Oxford, United Kingdom.
Chou
C Y
CY
Ellory
J C
JC
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D005260:Female; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D007038:Hypotonic Solutions / Q000494:pharmacology; D009579:Nitrobenzoates / Q000494:pharmacology; D011189:Potassium Chloride / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000502:physiology*; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics; D016196:S Phase / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D013654:Taurine / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism; D002583:Uterine Cervical Neoplasms; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*
D016588:Anticarcinogenic Agents; D007038:Hypotonic Solutions; D009579:Nitrobenzoates; D012414:Rubidium Radioisotopes; D013629:Tamoxifen; D013654:Taurine; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D011189:Potassium Chloride