We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
IP<sub>3</sub> receptor antagonist, 2-APB, attenuates cisplatin induced Ca<sup>2+</sup>-influx in HeLa-S3 cells and prevents activation of calpain and induction of apoptosis.
- Authors
Splettstoesser, F.; Florea, A.-M.; Büsselberg, D.
- Abstract
Background and purpose:Cisplatin drives specific types of tumour cells to apoptosis. In this study we investigate the involvement of intracellular calcium ([Ca2+]i) in triggering apoptosis in two different cell lines. As cisplatin is used for the treatment of several forms of cancer we choose HeLa-S3 and U2-OS as two examples of tumour cell lines.Experimental approach:Cisplatin (1nM–10μM) was applied to HeLa-S3 and U2-OS cells and [Ca2+]i measured with fluo-4, using laser scanning microscopy. Inositol-1,4,5-trisphosphate (IP3) receptors were visualized with immunostaining. Membrane conductances were measured with patch-clamp techniques. Levels of calpain and caspases were assessed by western blots and apoptotic cells were stained with Hoechst 33342 and counted.Key results:Cisplatin increases [Ca2+]i concentration-dependently in HeLa-S3 but not in U2-OS cells. This elevation of [Ca2+]i depended on extracellular Ca2+ but was reduced by the IP3 receptor blocker, 2-APB. This effect was not due to a Ca2+ release triggered by Ca2+ entry. Immunostaining showed IP3-receptors (type1-3) at the cellular membrane of HeLa-S3 cells, but not in U2-OS cells. Electrophysiological experiments showed an increased membrane conductance with cisplatin only when Ca2+ was present extracellularly. Increase of [Ca2+]i was related to the activation of calpain but not caspase-8 and triggered apoptosis in HeLa-S3 but not in U2-OS cells.Conclusions and implications:Our observations on the activation of IP3-receptors, calcium entry and apoptotic rate by cisplatin in specific carcinogenic cells might open new possibilities in the treatment of some forms of cancer.British Journal of Pharmacology (2007) 151, 1176–1186; doi:10.1038/sj.bjp.0707335; published online 25 June 2007
- Subjects
CISPLATIN; DRUG receptors; DRUG interactions; APOPTOSIS; PHARMACOLOGY
- Publication
British Journal of Pharmacology, 2007, Vol 151, Issue 8, p1176
- ISSN
0007-1188
- Publication type
Article
- DOI
10.1038/sj.bjp.0707335