Induction of the HSP70 gene promoter by various anticancer drugs

Abstract : HeLa cells containing the chloramphenicol acetyl transferase (CAT) gene under the control of the hsp70 promoter have been exposed in vitro to various anticancer drugs. Cisplatin induced CAT production with a dose-effect relationship at a non-cytotoxic dose, whereas no induction was detected with carboplatin. Etoposid induced a significant response at a cytotoxic concentration. The limited positive response with doxorubicin, daunomycin and mitoxantrone was not statistically significant. These chemicals are known to produce reactive oxygen species and induce apoptosis. No induction of the hsp70 promoter could be detected with the other cytostatic compounds that have been tested such as base analogues (5-fluorouracil, cytosine arabinoside 3'-MP), inhibitors of DNA synthesis (amethopterin, aminopterin), antimitotics (vinblastine, colchicine), and alkylating (streptozotocine, carboplatin, melphalan) or intercalating agents (bleomycin). In addition, the role of the transcription inhibitory activity of doxorubicin in this model is evidenced and the consequent question of the suitability of the reporter gene system is discussed. Our results suggest that specific genotoxic compounds are not able to induce the hsp70 promoter, and are in agreement with the concept that stimulation of HSP70 synthesis occurs through a biochemical process involving proteotoxicity.
Document type :
Journal articles
Complete list of metadatas

Cited literature [16 references]  Display  Hide  Download

https://hal-ineris.archives-ouvertes.fr/ineris-00961849
Contributor : Gestionnaire Civs <>
Submitted on : Thursday, March 20, 2014 - 3:26:06 PM
Last modification on : Friday, February 9, 2018 - 4:24:49 PM
Long-term archiving on : Friday, June 20, 2014 - 12:01:54 PM

File

1998-050b_post-print.pdf
Files produced by the author(s)

Identifiers

Collections

Citation

Selim Ait-Aissa, Jean-Marc Porcher, C. Kretz-Remy, G. Velarde, André-Patrick Arrigo, et al.. Induction of the HSP70 gene promoter by various anticancer drugs. Toxicology in Vitro, Elsevier, 1999, 13 (4-5), pp.651-655. ⟨10.1016/S0887-2333(99)00032-6⟩. ⟨ineris-00961849⟩

Share

Metrics

Record views

212

Files downloads

347