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- Title
POSSIBLE PARTICIPATION OF CHLORIDE ION CHANNELS IN ATP RELEASE FROM CANCER CELLS IN SUSPENSION.
- Authors
Nejime, Namie; Kagota, Satomi; Tada, Yukari; Nakamura, Kazuki; Hashimoto, Michio; Kunitomo, Masaru; Shinozuka, Kazumasa
- Abstract
1. Cancer cells must detach from the primary focus to initiate the process of metastasis. Previously, we demonstrated that intracellular Ca2+ levels are increased in endothelial cells in the presence of cancer cells and that ATP derived from these cells causes this increase. The present study clarifies the mechanism of ATP release from cancer cells by investigating the effects of Cl− channel inhibitors and other drugs on ATP release from human fibrosarcoma cells (HT-1080 cells). 2. Levels of extracellular ATP and its metabolites were measured using high-performance liquid chromatography (HPLC) with fluorescent detection. 3. Significantly more extracellular ATP was released by suspended than by adherent HT-1080 cells. The Cl− channel inhibitors 5-nitro-2-(3-phenylpropylamino) benzoic acid (100 µmol/L), gadolinium (100 µmol/L) and niflumic acid (100 µmol/L) all significantly inhibited ATP release from HT-1080 cells (1 × 103 /mL) to 39.7 ± 6.5, 28.5 ± 2.5 and 82.5 ± 4.1% of control, respectively. 4. Neither of the p-glycoprotein inhibitors (i.e. 50 µmol/L quinidine and 90 µmol/L verapamil) had any effect on ATP release from HT-1080 cells. The gap junction hemichannel inhibitor Gap26 (300 µmol/L) slightly, but significantly, decreased ATP release by approximately 20%. The gap junction inhibitor 18-α-glycyrrhetinic acid (10 µmol/L) tended to inhibit ATP release from HT-1080 cells, but the difference did not reach statistical significance. 5. These findings indicate that Cl− channels play the most important role in ATP release from detached cancer cells and that gap junction hemichannels are also associated with ATP release.
- Subjects
CHLORIDE channels; ADENOSINE triphosphate; CANCER cells; METASTASIS
- Publication
Clinical & Experimental Pharmacology & Physiology, 2009, Vol 36, Issue 3, p278
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/j.1440-1681.2008.05060.x