3D cell cultures, as a surrogate for animal models, enhance the diagnostic value of preclinical in vitro investigations by adding information on the tumour microenvironment : a comparative study of new dual-mode HDAC inhibitors

DOI zum Zitieren der Version auf EPub Bayreuth: https://doi.org/10.15495/EPub_UBT_00007020
URN to cite this document: urn:nbn:de:bvb:703-epub-7020-0

Title data

Bär, Sofia I. ; Biersack, Bernhard ; Schobert, Rainer:
3D cell cultures, as a surrogate for animal models, enhance the diagnostic value of preclinical in vitro investigations by adding information on the tumour microenvironment : a comparative study of new dual-mode HDAC inhibitors.
In: Investigational New Drugs. Vol. 40 (2022) Issue 5 . - pp. 953-961.
ISSN 1573-0646
DOI der Verlagsversion: https://doi.org/10.1007/s10637-022-01280-0

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Abstract

Anchorage-independent 3D-cultures of multicellular tumour spheroids (MCTS) and in vitro microtumours of cancer cells can provide upfront information on the effects of anticancer drug candidates, tantamount to that obtained from animal xenograft studies. Unlike 2D cancer cell cultures, 3D-models take into account the influence of the tumour microenvironment and the location dependence of drug effects and accumulation. We exemplified this by comparison of the effects of two new dual-mode anticancer agents, Troxbam and Troxham, and their monomodal congeners SAHA (suberoylanilide hydroxamic acid) and CA-4 (combretastatin A-4). We assessed the growth of MCTS of HCT116wt human colon carcinoma cells exposed to these compounds, as well as the spatial distribution of dead HCT116wt cells in these MCTS. Also, fluorescence imaging of live and fixed MCTS was used to assess the type of cellular death induced by test compounds. Furthermore, an innovative perfusion bioreactor system was used to grow microtumours in the presence or absence of test compounds. Both new investigational compounds led to significant reductions of the size of such MCTS and also of corresponding in vitro microtumours by inducing caspase-9 dependent apoptosis and elevated levels of reactive oxygen species. 3D multicellular tumour spheroids are easy to grow and employ for compound tests in the familiar well-plate set-up. Together with 3D microtumours grown at scaffolds in continuously perfused bioreactors they allow to study, early on in the course of drug evaluations, the communication of tumour cells with their microenvironment to an extent hitherto available only in animal experiments.

Further data

Item Type:	Article in a journal
Keywords:	Cancer research; Colon cancer; 3D cell culture; Tumour spheroids; Microtumours; HDACi
DDC Subjects:	500 Science > 540 Chemistry
Institutions of the University:	Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Chair Organic Chemistry I - Univ.-Prof. Dr. Rainer Schobert Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors
Language:	English
Originates at UBT:	Yes
URN:	urn:nbn:de:bvb:703-epub-7020-0
Date Deposited:	07 Jun 2023 08:36
Last Modified:	07 Jun 2023 08:37
URI:	https://epub.uni-bayreuth.de/id/eprint/7020

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