1995
DOI: 10.1038/bjc.1995.334
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Hyperthermia, thermotolerance and topoisomerase II inhibitors

Abstract: Summary The cytoxicity of both intercalating (m-AMSA) and non-intercalating (VP16, VM26) topoisomerase II-targeting drugs is thought to occur via trapping DNA topoisomerase II on DNA in the form of cleavable complexes. First, analysis of cleavable complexes (detected as DNA double-strand breaks) by pulsed-field gel electrophoresis confirmed the correlation between cleavable complex formation and cytotoxicity of three topoisomerase-targeting drugs in HeLa S3 cells (the order of effects being VM26> m-AMSA>VP16).… Show more

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Cited by 38 publications
(24 citation statements)
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“…Etoposide differs from almost all other cytostatics in that thermal enhancement of its effect has not been observed [2,4]. Tumour cells were even found to be protected from etoposide by heat [3,5]. We confirmed these observations when we found a merely insignificant reduction of colonies by hyperthermia of untreated cells as well as of cells treathed simultaneously with etoposide.…”
Section: Discussionsupporting
confidence: 81%
See 1 more Smart Citation
“…Etoposide differs from almost all other cytostatics in that thermal enhancement of its effect has not been observed [2,4]. Tumour cells were even found to be protected from etoposide by heat [3,5]. We confirmed these observations when we found a merely insignificant reduction of colonies by hyperthermia of untreated cells as well as of cells treathed simultaneously with etoposide.…”
Section: Discussionsupporting
confidence: 81%
“…For etoposide, this effect could never be demonstrated [2]. Some data show even a protective effect of heat against etoposide toxicity [3]. Studies with neuroblastoma cells regarding the effect of hyperthermia and drugs are lacking.…”
Section: Introductionmentioning
confidence: 99%
“…It has been reported that DNA topoisomerase II is vital for essential biological reactions, such as replication, transcription, and genetic recombination (45,46), and Nelson et al reported that mAMSA [4'-(9-acridinylamino) methane sulfonm-anisidide], an antitumor agent, inhibited topoisomerase II in mammals (47). Therefore, topoisomerase II inhibitors are effective anticancer agents, because topoisomerase II inactivation and inhibition have severe effects on cell survival (48,49).…”
Section: Discussionmentioning
confidence: 99%
“…The most remarkable component of this response is the massive transcriptional induction of several families of molecular chaperones including heat shock proteins (HSP) 27, 40, 60, 70, 90 and 110 15 . These molecular chaperones counter the triggering event in thermal cell killing and protein denaturation 7,8,16 . However, the mechanisms underlying thermotolerance are highly complex and involve a number of other components, in addition to the induction of expression of HSP molecular chaperones.…”
Section: Introductionmentioning
confidence: 99%