High-content drug screening in zebrafish xenografts reveals high efficacy of dual MCL-1/BCL-XL inhibition against Ewing sarcoma

Grissenberger, Sarah; Sturtzel, Caterina; Wenninger-Weinzierl, Andrea; Radic-Sarikas, Branka; Scheuringer, Eva; Bierbaumer, Lisa; Etienne, Vesnie; Némati, Fariba; Pascoal, Susana; Tötzl, Marcus; Tomazou, Eleni M.; Metzelder, Martin L.; Putz, Eva Maria; Decaudin, Didier; Delattre, Olivier; Surdez, Didier; Kovar, Heinrich; Halbritter, Florian; Distel, Martin

doi:10.1016/j.canlet.2022.216028

Cited by 8 publications

(3 citation statements)

References 51 publications

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“…Ednrba −/− b140 derive from the Kimmel lab and mitfa −/− b692 from the Raible lab. Xenotransplantation of zebrafish embryos (license GZ:333989‐2020‐4) was performed as previously described [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

“…Automated imaging of xenografted zebrafish was carried out as described by Grissenberger et al. [ 20 ] using an Operetta CLS high‐content imager [PerkinElmer, Waltham, MA, USA; 5× air objective, brightfield (40 ms, 10%), GFP (excitation: 460–490 nm at 100%, emission: 500–550 nm for 400 ms), tagRFP (excitation: 530–560 nm at 100%, emission: 570/650 nm for 400 ms), 23 planes with a distance of 25 μm]. Pictures were taken 1 and 2 days post injection (dpi), and cells present in the tail were manually counted using imagej .…”

Section: Methodsmentioning

confidence: 99%

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YB‐1 regulates mesothelioma cell migration via snail but not EGFR, MMP1, EPHA5 or PARK2

et al. 2023

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Pleural mesothelioma (PM) is characterized by rapid growth, local invasion, and limited therapeutic options. The multifunctional oncoprotein Y‐box‐binding protein‐1 (YB‐1) is frequently overexpressed in cancer and its inhibition reduces aggressive behavior in multiple tumor types. Here, we investigated the effects of YB‐1 on target gene regulation and PM cell behavior. Whereas siRNA‐mediated YB‐1 knockdown reduced cell motility, YB‐1 overexpression resulted in scattering, increased migration, and intravasation in vitro. Furthermore, YB‐1 stimulated PM cell spreading in zebrafish. Combined knockdown and inducible overexpression of YB‐1 allowed bidirectional control and rescue of cell migration, the pattern of which was closely followed by the mRNA and protein levels of EGFR and the protein level of snail, whereas the mRNA levels of MMP1, EPHA5, and PARK2 showed partial regulation by YB‐1. Finally, we identified snail as a critical regulator of YB‐1‐mediated cell motility in PM. This study provides insights into the mechanism underlying the aggressive nature of PM and highlights the important role of YB‐1 in this cancer. In this context, we found that YB‐1 closely regulates EGFR and snail, and, moreover, that YB‐1‐induced cell migration depends on snail.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

YB‐1 regulates mesothelioma cell migration via snail but not EGFR, MMP1, EPHA5 or PARK2

et al. 2023

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“…Nude mice are most commonly used for this type of experiment, but the research takes a long time and they are expensive. To overcome these shortcomings, an alternative animal model using the Danio rerio larvae is increasingly being used to test potential anti-cancer drugs [ 15 ]. The Danio rerio larvae model has numerous advantages, e.g., the ability to study a large number of individuals simultaneously, a shorter duration of the experiments, and a large number of experiments that can be carried out at affordable costs.…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Silico of Cholinesterases Inhibition and In Vitro and In Vivo Anti-Melanoma Activity Investigations of Extracts Obtained from Selected Berberis Species

Tuzimski,

Petruczynik,

Kaproń

et al. 2024

Molecules

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Berberis species have a long history of use in traditional Chinese medicine, Ayurvedic medicine, and Western herbal medicine. The aim of this study was the quantification of the main isoquinoline alkaloids in extracts obtained from various Berberis species by HPLC, in vitro and in silico determination of anti-cholinesterase activity, and in vitro and in vivo investigations of the cytotoxic activity of the investigated plant extracts and alkaloid standards. In particular, Berberis species whose activity had not been previously investigated were selected for the study. In the most investigated Berberis extracts, a high content of berberine and palmatine was determined. Alkaloid standards and most of the investigated plant extracts exhibit significant anti-cholinesterase activity. Molecular docking results confirmed that both alkaloids are more favourable for forming complexes with acetylcholinesterase compared to butyrylcholinesterase. The kinetic results obtained by HPLC-DAD indicated that berberine noncompetitively inhibited acetylcholinesterase, while butyrylcholinesterase was inhibited in a mixed mode. In turn, palmatine exhibited a mixed inhibition of acetylcholinesterase. The cytotoxic activity of berberine and palmatine standards and plant extracts were investigated against the human melanoma cell line (A375). The highest cytotoxicity was determined for extract obtained from Berberis pruinosa cortex. The cytotoxic properties of the extract were also determined in the in vivo investigations using the Danio rerio larvae xenograft model. The obtained results confirmed a significant effect of the Berberis pruinosa cortex extract on the number of cancer cells in a living organism. Our results showed that extracts obtained from Berberis species, especially the Berberis pruinosa cortex extract, can be recommended for further in vivo experiments in order to confirm the possibility of their application in the treatment of neurodegenerative diseases and human melanoma.

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Exploration and optimisation of structure-activity relationships of new triazole-based C-terminal Hsp90 inhibitors towards in vivo anticancer potency

Dernovšek,

Zajec,

Poje

et al. 2024

Biomedicine & Pharmacotherapy

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High-content drug screening in zebrafish xenografts reveals high efficacy of dual MCL-1/BCL-XL inhibition against Ewing sarcoma

Cited by 8 publications

References 51 publications

YB‐1 regulates mesothelioma cell migration via snail but not EGFR, MMP1, EPHA5 or PARK2

YB‐1 regulates mesothelioma cell migration via snail but not EGFR, MMP1, EPHA5 or PARK2

In Vitro and In Silico of Cholinesterases Inhibition and In Vitro and In Vivo Anti-Melanoma Activity Investigations of Extracts Obtained from Selected Berberis Species

Exploration and optimisation of structure-activity relationships of new triazole-based C-terminal Hsp90 inhibitors towards in vivo anticancer potency

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