Related Experiment Videos
Resistance to etoposide induced by three glucose-regulated stresses in Chinese hamster ovary cells
C S Hughes1, J W Shen, J R Subjeck
1Division of Radiation Biology, Roswell Park Memorial Institute, Buffalo, New York 14263.
Abstract:
The induction of glucose-regulated proteins by a variety of specific inducers leads to an increase in resistance to Adriamycin (Shen et al., Proc. Natl., Acad. Sci. USA, 84: 3278, 1987). In this study we examine several additional agents for cross-resistance induced during a glucose-regulated response in an attempt to better define the mechanism through which this phenomenon occurs. When anoxia, calcium ionophore A23187, or 2-deoxyglucose are used, a substantial resistance is obtained against the topoisomerase II-targeted agent, etoposide. Partial resistance is induced against vincristine and actinomycin D. Glucose-regulated protein inducers do not substantially alter cellular response to either bleomycin or radiation. In the case of mitomycin C there is a cellular sensitization with anoxia and 2-deoxyglucose while calcium ionophore A23187 had no effect on survival. This study suggests that the resistance obtained during a glucose-regulated response against etoposide and Adriamycin may involve topoisomerase II.
Insights
Glucose-regulated proteins induce resistance to Adriamycin and etoposide, suggesting a role for topoisomerase II in this cellular defense mechanism against chemotherapy drugs.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Glucose-regulated proteins (GRPs) are known to confer resistance to Adriamycin.
- The precise mechanism underlying this cross-resistance phenomenon remains incompletely understood.
Purpose of the Study:
- To investigate additional agents that induce cross-resistance during a glucose-regulated response.
- To further elucidate the molecular mechanisms involved in GRP-mediated drug resistance.
Main Methods:
- Cells were treated with various inducers of glucose-regulated proteins, including anoxia, calcium ionophore A23187, and 2-deoxyglucose.
- Cellular responses to a panel of chemotherapeutic agents (etoposide, vincristine, actinomycin D, bleomycin, radiation, mitomycin C) were assessed following induction.
Main Results:
- Substantial resistance to etoposide (a topoisomerase II inhibitor) was observed with anoxia, A23187, and 2-deoxyglucose.
- Partial resistance was induced against vincristine and actinomycin D.
- No significant alteration in cellular response was noted for bleomycin or radiation.
- Mitomycin C showed cellular sensitization with anoxia and 2-deoxyglucose, but not with A23187.
Conclusions:
- The glucose-regulated response confers cross-resistance to topoisomerase II-targeted agents like etoposide and Adriamycin.
- Topoisomerase II likely plays a significant role in the resistance mechanism induced by GRPs.