Intrinsic differences in cisplatin sensitivity of head and neck cancer cell lines: Correlation to lysosomal pH.

Abstract

BACKGROUND:

Cisplatin treatment is beneficial for approximately 20% of patients with head and neck squamous cell carcinoma (HNSCC). Tools to predict the clinical outcome and evaluate intrinsic cisplatin sensitivity are, therefore, required.

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.

• 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)

Chemical References

• Cisplatin

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