Evidence of cisplatin-induced senescent-like growth arrest in nasopharyngeal carcinoma cells.
Cellular senescence is a programmed cell response leading to growth arrest in human diploid fibroblasts. We have shown that a nasopharyngeal carcinoma cell line, CNE1, following treatment by the DNA-damaging agent cisplatin, can undergo cellular senescent-like growth arrest, similar to fibroblasts, judged by cellular morphological changes and the expression of senescence-associated beta-galactosidase (SA-beta-gal). This senescent-like change was dose related; at 0.5 microgram/ml, the percentage of cisplatin-induced SA-beta-gal-positive cells was high (40-96%), and the staining was intense. Higher doses (1.0 and 2.0 micrograms/ml) of cisplatin induced lower SA-beta-gal expression (30-70%), and the process was irreversible. This cisplatin-induced cellular senescent-like response was not due to the inhibition of telomerase activity. Our results indicate that cellular senescent-like pathways exist in nasopharyngeal carcinoma cells and can be induced by cisplatin. Our evidence suggests that cellular senescent-like responses may be a cellular protection mechanism that acts differently in response to different degrees of cellular damage.
Wang
X
X
Department of Pathology, University of Hong Kong, Queen Mary Hospital, People's Republic of China.
Wong
S C
SC
Pan
J
J
Tsao
S W
SW
Fung
K H
KH
Kwong
D L
DL
Sham
J S
JS
Nicholls
J M
JM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers; D002453:Cell Cycle / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001616:beta-Galactosidase / Q000378:metabolism*
D000970:Antineoplastic Agents; D015415:Biomarkers; D001616:beta-Galactosidase; D002945:Cisplatin