6-Bromoindirubin-3′oxime (BIO) decreases proliferation and migration of canine melanoma cell lines

Chon, Esther; Flanagan, Brandi; Rodrigues, Lucas Campos de Sá; Piskun, Caroline M.; Stein, Timothy J.

doi:10.1016/j.tvjl.2014.07.012

Cited by 11 publications

(3 citation statements)

References 43 publications

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“…BIO is an inhibitor that targets the activity of Glycogen synthase kinase-3 (GSK-3). GSK-3 is a serine threonine kinase which is involved in many cellular processes in glioma cells including cell migration (Chon et al 2015). Even though this inhibitor has been the basis of many studies to target cell migration (Yu & Zhao, 2016, Zhao et al 2019) its mode of action via GSK-3 regulation is still not known, especially in 3D spheroids.…”

Section: Discussionmentioning

confidence: 99%

‘Cloudbuster’: a Python-based open source application for three-dimensional reconstruction and quantification of stacked biological imaging samples

et al. 2022

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Three-dimensional (3D) spheroid cultures are generating increasing interest in cancer research, e.g. for the evaluation of pharmacological effects of novel small molecule inhibitors. This is mainly due to the fact that such 3D structures reflect physiological characteristics of tumours and the cellular microenvironments they reside in more faithfully than two-dimensional (2D) cell cultures; in addition, they allow the reduction of animal experiments while providing significantly relevant human-based models. Quantification of such organoid structures as well as the mainly slice-based acquisition and thus forced 2D representation of 3D spheroids provide a challenge for the interpretation of the associated generated data. Here, we provide a novel open-source workflow to reconstruct a 3D entity from slice-recorded microscopical images with or without treatment with anti-migratory small molecule inhibitors. This reconstruction produces distinct point clouds as basis for subsequent comparison of basic readout parameters using average computer processor, memory and graphics resources within an acceptable time frame. We were able to validate the usefulness of this workflow using 3D data generated by various imaging techniques, including z -stacks from confocal microscopy and histochemically labelled spheroid sectioning, and demonstrate the possibility to accurately characterize inhibitor effects in great detail.

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Section: Discussionmentioning

confidence: 99%

‘Cloudbuster’: a Python-based open source application for three-dimensional reconstruction and quantification of stacked biological imaging samples

et al. 2022

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“…It was reported that BIO promoted the proliferation of human periodontal ligament stem cells (PDLSCs) [ 40 ], rat marrow-derived mesenchymal stem cells [ 41 ], and rat cardiomyocytes [ 42 ]. In contrast, other studies demonstrated that BIO decreased cell proliferation in stem cells isolated from human exfoliated deciduous teeth [ 40 ], hDPSCs [ 43 ], ovarian cancer cells [ 44 ], a mouse myoblast cell line [ 45 ], canine BMSCs [ 46 ], and canine melanoma cell lines [ 47 ]. Similarly, the effect of Wnt on cell migration remains controversial.…”

Section: Discussionmentioning

confidence: 99%

6-Bromoindirubin-3′-Oxime Regulates Colony Formation, Apoptosis, and Odonto/Osteogenic Differentiation in Human Dental Pulp Stem Cells

Kornsuthisopon

Rochanavibhata

Nowwarote

et al. 2022

IJMS

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6-bromoindirubin-3′-oxime (BIO) is a candidate small molecule that effectively modulates Wnt signalling owing to its stable property. The present study investigated the influence of BIO on the odonto/osteogenic differentiation of human dental pulp stem cells (hDPSCs). hDPSCs were treated with 200, 400, or 800 nM BIO, and the effects on hDPSC responses and osteogenic differentiation were assessed. BIO-mediated Wnt activation was confirmed by β-catenin nuclear translocation detected by immunofluorescence staining. BIO attenuated colony formation and cell migration determined by in vitro wound-healing assay. BIO increased early apoptotic cell population evaluated using flow cytometry. For osteogenic induction, BIO promoted alkaline phosphatase (ALP) activity and mineralisation in a dose-dependent manner. ALP, RUNX2, OCN, OSX, ANKH, DMP1, and DSPP mRNA expression were significantly upregulated. The OPG/RANKL expression ratio was also increased. Further, BIO attenuated adipogenic differentiation as demonstrated by decreased lipid accumulation and adipogenic-related gene expression. Bioinformatic analysis of RNA sequencing data from the BIO-treated hDPSCs revealed that BIO modulated pathways related to autophagy and actin cytoskeleton regulation. These findings demonstrated that BIO treatment promoted hDPSC osteogenic differentiation. Therefore, this small molecule is a strong candidate as a bioactive molecule to enhance dentin repair.

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“…Activation of the wnt/β-catenin pathway can upregulate c-Myc expression in various cells ( Li et al, 2012 ; Zhang et al, 2012 ). In addition, BIO has been shown to influence cell proliferation and stemness in various cells, including cancer cells ( Chon et al, 2015 ; Liu et al, 2017 ). In this study, we identified BIO as a strong upregulator of c-Myc expression without any significant effect on cell proliferation or apoptosis in OACM5.1C esophageal cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of the Cyclin-Dependent Kinase Inhibitor Flavopiridol on c-Myc Overexpressing Esophageal Cancer

et al. 2021

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Tumors with elevated c-Myc expression often exhibit a highly aggressive phenotype, and c-Myc amplification has been shown to be frequent in esophageal cancer. Emerging data suggests that synthetic lethal interactions between c-Myc pathway activation and small molecules inhibition involved in cell cycle signaling can be therapeutically exploited to preferentially kill tumor cells. We therefore investigated whether exploiting elevated c-Myc expression is effective in treating esophageal cancer with the CDK inhibitor flavopiridol. We found frequent overexpression of c-Myc in human esophageal cancer cell lines and tissues. c-Myc overexpression correlated with accelerated esophageal cancer subcutaneous xenograft tumor growth. Esophageal cancer cells with elevated c-Myc expression were found preferentially more sensitive to induction of apoptosis by the CDK inhibition flavopiridol compared to esophageal cancer cells with lower c-Myc expression. In addition, we observed that flavopiridol alone or in combination with the chemotherapeutic agent nanoparticle albumin-bound paclitaxel (NPT) or in combinations with the targeted agent BMS-754807 significantly inhibited esophageal cancer cell proliferation and subcutaneous xenograft tumor growth while significantly enhancing overall mice survival. These results indicate that aggressive esophageal cancer cells with elevated c-Myc expression are sensitive to the CDK inhibitor flavopiridol, and that flavopiridol alone or in combination can be a potential therapy for c-Myc overexpressing esophageal cancer.

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6-Bromoindirubin-3′oxime (BIO) decreases proliferation and migration of canine melanoma cell lines

Cited by 11 publications

References 43 publications

‘Cloudbuster’: a Python-based open source application for three-dimensional reconstruction and quantification of stacked biological imaging samples

‘Cloudbuster’: a Python-based open source application for three-dimensional reconstruction and quantification of stacked biological imaging samples

6-Bromoindirubin-3′-Oxime Regulates Colony Formation, Apoptosis, and Odonto/Osteogenic Differentiation in Human Dental Pulp Stem Cells

Therapeutic Potential of the Cyclin-Dependent Kinase Inhibitor Flavopiridol on c-Myc Overexpressing Esophageal Cancer

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