Abstract
Heat shock proteins have been reported to confer resistance to certain antineoplastic drugs. We investigated the impact of hsp70 overexpression on the efficacy of two new anti-cancer drugs, topotecan and gemcitabine. We used the fibrosarcoma WEHI-S cells stably transfected to overexpress the hsp70 cDNA from the constitutive SV40 promoter and appropriate control cells. After topotecan and gemcitabine treatment hsp70-overexpressing cells showed a marked elevation in cell survival, suggesting that hsp70 overexpression was sufficient to confer resistance to the drugs. In addition, hsp70-overexpressing cells were capable of starting cell proliferation after treatment with drug dosages that were lethal to control cells. Our results demonstrate that hsp70 overexpression represents a possible cause of drug resistance. In order to transfer these data to tumour cells constitutively expressing stress hsp70 due to the constitutive activity of the original hsp70 promoter we sought to supress the heat shock response pathway by the natural flavonoid quercetin, known to inactivate the heat shock transcription factor (HSF). Using a suitable cell line, we demonstrated the sensitising activity of quercetin. We found that antineoplastic drug concentrations exerting cytotoxic activity were markedly lower when cells were pretreated with quercetin. Concomitantly, hsp70 expression was strongly down-regulated under quercetin treatment. Our data indicate that quercetin may be useful as a sensitiser in chemotherapeutically treated patients suffering from hsp70-overexpressing tumours.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sliutz, G., Karlseder, J., Tempfer, C. et al. Drug resistance against gemcitabine and topotecan mediated by constitutive hsp70 overexpression in vitro: implication of quercetin as sensitiser in chemotherapy. Br J Cancer 74, 172–177 (1996). https://doi.org/10.1038/bjc.1996.334
Issue Date:
DOI: https://doi.org/10.1038/bjc.1996.334
This article is cited by
-
HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells
Cell Death & Disease (2022)
-
microRNA-mediated resistance to hypoglycemia in the HepG2 human hepatoma cell line
BMC Cancer (2016)
-
Mechanisms of Rutin Pharmacological Action (Review)
Pharmaceutical Chemistry Journal (2014)
-
HSP70 desensitizes osteosarcoma cells to baicalein and protects cells from undergoing apoptosis
Apoptosis (2014)
-
HSP90: Chaperone-me-not
Pathology & Oncology Research (2013)