Gutenberg Open Science: Accumulation of temozolomide-induced apoptosis, senescence and DNA damage by metronomic dose schedule : a proof-of-principle study with glioblastoma cells

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8667

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DC Field	Value	Language
dc.contributor.author	Beltzig, Lea	-
dc.contributor.author	Stratenwerth, Björn	-
dc.contributor.author	Kaina, Bernd	-
dc.date.accessioned	2023-02-13T08:18:03Z	-
dc.date.available	2023-02-13T08:18:03Z	-
dc.date.issued	2021	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/8683	-
dc.description.abstract	Temozolomide (TMZ), a first-line drug in glioma therapy, targets the tumor DNA at various sites. One of the DNA alkylation products is O6-methylguanine (O6MeG), which is, in the low dose range of TMZ, responsible for nearly all genotoxic and cytotoxic effects relevant for cancer therapy. There is, however, a dispute regarding whether the TMZ concentration in the tumor tissue in patients is sufficient to elicit a significant cytotoxic or cytostatic response. Although treatment with TMZ occurs repeatedly with daily doses (metronomic dose schedule) and in view of the short half-life of the drug it is unclear whether doses are accumulating. Here, we addressed the question whether repeated low doses elicit similar effects in glioblastoma cells than a high cumulative dose. We show that repeated treatments with a low dose of TMZ (5 × 5 µM) caused an accumulation of cytotoxicity through apoptosis, cytostasis through cellular senescence, and DNA double-strand breaks, which was similar to the responses induced by a single cumulative dose of 25 µM TMZ. This finding, together with the previously reported linear dose–response curves, support the notion that TMZ is able to trigger a significant cytotoxic and cytostatic effect in vivo if the low-dose metronomic schedule is applied.	en_GB
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Accumulation of temozolomide-induced apoptosis, senescence and DNA damage by metronomic dose schedule : a proof-of-principle study with glioblastoma cells	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-8667	-
jgu.type.contenttype	Scientific article	de
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Cancers	de
jgu.journal.volume	13	de
jgu.journal.issue	24	de
jgu.pages.alternative	6287	de
jgu.publisher.year	2021	-
jgu.publisher.name	MDPI	de
jgu.publisher.place	Basel	de
jgu.publisher.issn	2072-6694	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.3390/cancers13246287	de
jgu.organisation.ror	https://ror.org/023b0x485	-
jgu.subject.dfg	Lebenswissenschaften	de
Appears in collections:	JGU-Publikationen

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