The RosetteSep™ Human Custom Cocktail is designed to deplete unwanted cells from fresh whole blood by negative selection. When centrifuged over a buoyant density medium such as Lymphoprep™ (Catalog #07801), the unwanted cells pellet along with the RBCs. The cells of interest are present as an enriched population at the interface between the plasma and the buoyant density medium. STEMCELL Technologies offers a wide selection of antibodies for custom separation and will work with you to isolate a cell type of interest. Please contact our technical support team at techsupport@stemcell.com for more information.
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Combination of 5-fluorouracil and thymoquinone targets stem cell gene signature in colorectal cancer cells. Cell death {\&} disease 2019
Abstract
Cancer stem cells (CSCs) residing in colorectal cancer tissues have tumorigenic capacity and contribute to chemotherapeutic resistance and disease relapse. It is well known that the survival of colorectal CSCs after 5-fluorouracil (5-FU)-based therapy leads to cancer recurrence. Thus CSCs represent a promising drug target. Here, we designed and synthesized novel hybrid molecules linking 5-FU with the plant-derived compound thymoquinone (TQ) and tested the potential of individual compounds and their combination to eliminate colorectal CSCs. Both, Combi and SARB hybrid showed augmented cytotoxicity against colorectal cancer cells, but were non-toxic to organoids prepared from healthy murine small intestine. NanoString analysis revealed a unique signature of deregulated gene expression in response to the combination of TQ and 5-FU (Combi) and SARB treatment. Importantly, two principle stem cell regulatory pathways WNT/{\ss}-Catenin and PI3K/AKT were found to be downregulated after Combi and hybrid treatment. Furthermore, both treatments strikingly eliminated CD133+ CSC population, accompanying the depleted self-renewal capacity by eradicating long-term propagated 3D tumor cell spheres at sub-toxic doses. In vivo xenografts on chicken eggs of SARB-treated HCT116 cells showed a prominent nuclear {\ss}-Catenin and E-cadherin staining. This was in line with the reduced transcriptional activity of {\ss}-Catenin and diminished cell adhesion under SARB exposure. In contrast to 5-FU, both, Combi and SARB treatment effectively reduced the angiogenic capacity of the remaining resistant tumor cells. Taken together, combination or hybridization of single compounds target simultaneously a broader spectrum of oncogenic pathways leading to an effective eradication of colorectal cancer cells.
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