Abstract | BACKGROUND: METHODS:
Cisplatin sensitivity, lysosomal pH, and cell death pathway was studied in 5 HNSCC lines and compared with normal oral keratinocytes. RESULTS: We identified a linear relationship between lysosomal pH and cisplatin sensitivity. Reduced lysosomal acidification was correlated to decreased expression of the V(0)V(1)-ATPase B2 subunit, which is part of the lysosomal acidifying complex. Cisplatin caused apoptosis accompanied by lysosomal membrane permeabilization, and inhibition of lysosomal proteases ( cathepsins) partly prevented cell death. CONCLUSION:
Cisplatin-induced apoptosis of HNSCC is more efficient in cell lines with low lysosomal pH and is mediated by the release of lysosomal content. Lysosomal pH and expression of V(0)V(1)-ATPase subunits are possible future markers of intrinsic cisplatin sensitivity.
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Authors | Cathrine Nilsson, Karin Roberg, Roland C Grafström, Karin Ollinger |
Journal | Head & neck
(Head Neck)
Vol. 32
Issue 9
Pg. 1185-94
(Sep 2010)
ISSN: 1097-0347 [Electronic] United States |
PMID | 20029982
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Apoptosis
(drug effects)
- Blotting, Western
- Carcinoma, Squamous Cell
(drug therapy, pathology)
- Cell Death
(drug effects)
- Cell Line, Tumor
(drug effects)
- Cisplatin
(pharmacology)
- Drug Resistance, Neoplasm
- Fluorescent Antibody Technique
- Head and Neck Neoplasms
(drug therapy, pathology)
- Humans
- Hydrogen-Ion Concentration
- Lysosomes
(drug effects, metabolism)
- Reference Values
- Sensitivity and Specificity
- Tumor Cells, Cultured
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