PUBLICATION

Preclinical Assessment of the Bioactivity of the Anticancer Coumarin OT48 by Spheroids, Colony Formation Assays, and Zebrafish Xenografts

Authors
Lee, J.Y., Mazumder, A., Diederich, M.
ID
ZDB-PUB-180717-7
Date
2018
Source
Journal of visualized experiments : JoVE   (136): (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals
  • Coumarins/pharmacology
  • Coumarins/therapeutic use*
  • Heterografts
  • Spheroids, Cellular/metabolism*
  • Zebrafish
PubMed
30010672 Full text @ J. Vis. Exp.
Abstract
In vitro and in vivo pre-clinical screening of novel therapeutic agents are an essential tool in cancer drug discovery. Although human cancer cell lines respond to therapeutic compounds in 2D (dimensional) monolayer cell cultures, 3D culture systems were developed to understand the efficacy of drugs in more physiologically relevant models. In recent years, a paradigm shift was observed in pre-clinical research to validate the potency of new molecules in 3D culture systems, more precisely mimicking the tumor microenvironment. These systems characterize the disease state in a more physiologically relevant manner and help to gain better mechanistic insight and understanding of the pharmacological potency of a given molecule. Moreover, with the current trend in improving in vivo cancer models, zebrafish has emerged as an important vertebrate model to assess in vivo tumor formation and study the effect of therapeutic agents. Here, we investigated the therapeutic efficacy of hydroxycoumarin OT48 alone or in combination with BH3 mimetics in lung cancer cell line A549 by using three different 3D culture systems including colony formation assays (CFA), spheroid formation assay (SFA) and in vivo zebrafish xenografts.
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Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
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Mapping