Document Detail

Glucose-regulated stresses confer resistance to VP-16 in human cancer cells through a decreased expression of DNA topoisomerase II.
MedLine Citation:
PMID:  8704275     Owner:  NLM     Status:  MEDLINE    
Glucose-regulated proteins (GRPs) are induced in cells by a variety of stress conditions such as treatment with 2-deoxyglucose, glucosamine, or the calcium ionophore A23187. We found that resistance to topoisomerase II (topo II) inhibitors, VP-16 and adriamycin, was induced by these treatments in human colon cancer HT-29 cells. Similar VP-16 resistance occurred in human ovarian cancer A2780 and breast cancer MCF-7 cells. The VP-16 resistance was reversible, since the sensitivity of the cells to VP-16 recovered within 24 h after the stresses were removed. Western blotting analysis showed that under these stress conditions the cellular contents of topo II alpha were decreased. The decreased expression of topo II was reversed to control levels within 24 h following removal of the stresses. The decrease in topo II levels under the stress conditions correlated well with the induction of GRP78 and 94. The close correlation between topo II and GRPs suggests that topo II is a protein sensitive to the glucose-regulated stresses. Since hypoxia and nutrient deprivation, which are also GRP-inducing conditions, could occur naturally in the solid tumors, the stress-associated cellular resistance through decrease in topo II levels may be a mechanism of the natural resistance of the solid tumors to topo II-directed chemotherapy.
J Yun; A Tomida; K Nagata; T Tsuruo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology research     Volume:  7     ISSN:  0965-0407     ISO Abbreviation:  Oncol. Res.     Publication Date:  1995  
Date Detail:
Created Date:  1996-09-06     Completed Date:  1996-09-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9208097     Medline TA:  Oncol Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  583-90     Citation Subset:  IM    
Laboratory of Biomedical Research, University of Tokyo, Japan.
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MeSH Terms
Antineoplastic Agents, Phytogenic / pharmacology*
Calcimycin / pharmacology
DNA Topoisomerases, Type II / antagonists & inhibitors*
Deoxyglucose / pharmacology
Drug Resistance
Etoposide / pharmacology*
HSP70 Heat-Shock Proteins / physiology*
Membrane Proteins / physiology*
Tumor Cells, Cultured
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/HSP70 Heat-Shock Proteins; 0/Membrane Proteins; 0/glucose-regulated proteins; 154-17-6/Deoxyglucose; 33419-42-0/Etoposide; 52665-69-7/Calcimycin; EC Topoisomerases, Type II

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