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Inhibition of N ‐linked glycosylation by tunicamycin enhances sensitivity to cisplatin in human head‐and‐neck carcinoma cells
Author(s) -
Noda Ichiro,
Fujieda Shigeharu,
Seki Mizue,
Tanaka Nobuyuki,
Sunaga Hiroshi,
Ohtsubo Toshio,
Tsuzuki Hideaki,
Fan GuoKang,
Saito Hitoshi
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990118)80:2<279::aid-ijc18>3.0.co;2-n
Subject(s) - cisplatin , tunicamycin , in vivo , apoptosis , in vitro , head and neck squamous cell carcinoma , mtt assay , cell culture , cancer research , microbiology and biotechnology , biology , chemotherapy , medicine , cancer , biochemistry , head and neck cancer , genetics , unfolded protein response
Tunicamycin (TM), a naturally occurring antibiotic, blocks the first step in the biosynthesis of N ‐linked oligosaccharides in cells. In this study, we investigated whether changes in N ‐linked glycosylation affect the sensitivity of head‐and‐neck carcinoma cell lines to cis ‐diaminedichloroplatinum(II) (cisplatin) in vitro and in vivo . In vitro treatment of the IMC‐3 and KB cell lines with TM significantly decreased the 50% inhibitory concentration (IC 50 ) of cisplatin, as determined by the MTT assay (24.15 to 10.97 μg/ml, p < 0.05). In addition, TM significantly decreased the IC 50 of cisplatin against established cisplatin‐resistant IMC‐3/CR cells (>100 to 14.4 μg/ml, p < 0.05) to levels similar to those against parental IMC‐3 cells. TM treatment decreased the number of Con A‐ and L‐PHA‐binding sites on the surface of tumor cells but had no effect on the intracellular platinum concentration. Induction of apoptosis in vitro by TM plus cisplatin in combination was increased compared with that by cisplatin alone. Furthermore, in vivo administration of TM plus cisplatin in combination significantly inhibited local tumor growth in the cisplatin‐resistant in vivo C3H/He mouse model as compared with the control group ( p < 0.05) and increased in vivo apoptosis of tumor cells. Our results suggest that the manipulation of glycosylation by TM in tumor cells might be a useful therapeutic strategy for successful chemotherapy using cisplatin against head‐and‐neck cancer. Int. J. Cancer80:279–284, 1999. © 1999 Wiley‐Liss, Inc.