Neutron radiation enhances cisplatin cytotoxicity independently of apoptosis in human head and neck carcinoma cells

Citation
He. Kim et al., Neutron radiation enhances cisplatin cytotoxicity independently of apoptosis in human head and neck carcinoma cells, CLIN CANC R, 6(10), 2000, pp. 4142-4147
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
6
Issue
10
Year of publication
2000
Pages
4142 - 4147
Database
ISI
SICI code
1078-0432(200010)6:10<4142:NRECCI>2.0.ZU;2-8
Abstract
Recent advances in combined modality treatment of locally advanced head and neck cancer have improved local and regional disease control and survival with better functional outcome, However, the local and regional failure rat e after radiation therapy is still high for tumors that respond poorly to c isplatin-based neoadjuvant chemotherapy. This clinical observation suggests a common biological mechanism for resistance to cisplatin and photon irrad iation. In this report, we investigated the molecular basis underlying cisp latin resistance in head and neck squamous carcinoma (HNSCC) cells and aske d if fast neutron radiation enhances cisplatin cytotoxicity in cisplatin-re sistant cells, We found that cisplatin sensitivity correlates with caspase induction, a cysteine proteinase family known to initiate the apoptotic cel l death pathway, suggesting that apoptosis may be a critical determinant fo r cisplatin cytotoxicity, Neutron radiation effectively enhanced cisplatin cytotoxicity in HNSCCs including cisplatin-resistant cells, whereas photon radiation had little effect on cisplatin cytotoxicity. Interestingly, neutr on-enhanced cisplatin cytotoxicity was associated neither with apoptosis no r with cell cycle regulation, as determined by caspase activity assay, anne xin V staining, and flow cytometric analysis, Taken together, the present s tudy provides a molecular insight into cisplatin resistance and may also pr ovide a basis for more effective multimodality protocols involving neutron radiation for patients with locally advanced head and neck cancer.