Induction of the hsp70 gene promoter by various anticancer drugs

HeLa cells containing the chloramphenicol acetyl transferase (CAT) gene und er the control of the hsp70 promoter have been exposed in vitro to various anticancer drugs. Cisplatin induced CAT production with a dose-effect relat ionship at a non-cytotoxic dose, whereas no induction was detected with car boplatin. Etoposid induced a significant response at a cytoxic concentratio n. The limited positive response with doxorubicin, daunomycin and mitoxantr one was nor statistically significant. these chemicals are known to produce reactive oxygen species and induce apoptosis. No induction of the hsp70 pr omoter 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 (vi nblastine, colchicine), and alkylating (streptozotocine, carboplatin, melph alan) or intercalating agents (bleomycin). In addition, the role of thr tra nscription inhibitory activity of doxorubicin in this model is evidenced an d the consequent question of the suitability of the reporter gene system is discussed. Our results suggest that specific genotoxic compounds are not a ble to induce the hsp70 promoter, and are in agreement with the concept tha t stimulation of HSP70 synthesis occurs through a biochemical process invol ving proteotoxicity. (C) 1999 Elsevier Science Ltd. All rights reserved.