Upregulation of β-Galactosidase (β-Gal) has been generally found in primary ovarian cancer cells, making the intra-cellular β-Gal as a valuable biomarker for related tumors. In this study, we ...synthesized an iminocoumarin based covalent-assembly probe, Gal–IC–2, which has been designed to be activated by β-Gal and then rapidly afford to a fluorescent chromophore via a covalent-assembly mechanism with red emission for specific and sensitive detection of β-Gal activity. Gal–IC–2 showed significant fluorescence enhancement and a large Stokes shift in the presence of recombinant β-Gal, and the detection limit of this probe was 1.97 × 10−2 UmL−1. Notably, Gal–IC–2 also exhibits great stability in a broad pH range and is capable of detecting the reactivity of β-Gal in ovarian cancer cells. This is the first report, to the best of our knowledge, describing a covalent-assembly red-emitting probe for the detection and imaging of β-Gal both in vitro and in ovarian cancer cells.
The first example of red-emitting covalent-assembly fluorescent probe for β-galactosidase was designed and synthesized. This probe can detect the activity of β-galactosidase both in vitro and in ovarian cancer cells with fast and high fluorescent response. Display omitted
•A self-covalent-assembly probe for detecting β-Gal is first reported here.•Gal–IC–2 is a red-emitting probe exhibiting great stability in a broad pH range.•In the presence of β-Gal, Gal–IC–2 shows significant fluorescence enhancement.•Gal–IC–2 can be applied to monitor endogenous β-Gal activity.
Cancer metabolism: looking forward Martínez-Reyes, Inmaculada; Chandel, Navdeep S
Nature reviews. Cancer,
10/2021, Letnik:
21, Številka:
10
Journal Article
Recenzirano
Tumour initiation and progression requires the metabolic reprogramming of cancer cells. Cancer cells autonomously alter their flux through various metabolic pathways in order to meet the increased ...bioenergetic and biosynthetic demand as well as mitigate oxidative stress required for cancer cell proliferation and survival. Cancer driver mutations coupled with environmental nutrient availability control flux through these metabolic pathways. Metabolites, when aberrantly accumulated, can also promote tumorigenesis. The development and application of new technologies over the last few decades has not only revealed the heterogeneity and plasticity of tumours but also allowed us to uncover new metabolic pathways involved in supporting tumour growth. The tumour microenvironment (TME), which can be depleted of certain nutrients, forces cancer cells to adapt by inducing nutrient scavenging mechanisms to sustain cancer cell proliferation. There is growing appreciation that the metabolism of cell types other than cancer cells within the TME, including endothelial cells, fibroblasts and immune cells, can modulate tumour progression. Because metastases are a major cause of death of patients with cancer, efforts are underway to understand how metabolism is harnessed by metastatic cells. Additionally, there is a new interest in exploiting cancer genetic analysis for patient stratification and/or dietary interventions in combination with therapies that target metabolism. In this Perspective, we highlight these main themes that are currently under investigation in the context of in vivo tumour metabolism, specifically emphasizing questions that remain unanswered.
Single-cell analyses have revealed extensive heterogeneity between and within human tumours
, but complex single-cell phenotypes and their spatial context are not at present reflected in the ...histological stratification that is the foundation of many clinical decisions. Here we use imaging mass cytometry
to simultaneously quantify 35 biomarkers, resulting in 720 high-dimensional pathology images of tumour tissue from 352 patients with breast cancer, with long-term survival data available for 281 patients. Spatially resolved, single-cell analysis identified the phenotypes of tumour and stromal single cells, their organization and their heterogeneity, and enabled the cellular architecture of breast cancer tissue to be characterized on the basis of cellular composition and tissue organization. Our analysis reveals multicellular features of the tumour microenvironment and novel subgroups of breast cancer that are associated with distinct clinical outcomes. Thus, spatially resolved, single-cell analysis can characterize intratumour phenotypic heterogeneity in a disease-relevant manner, with the potential to inform patient-specific diagnosis.
Metastatic pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid tumours despite the use of multi-agent conventional chemotherapy regimens. Such poor outcomes have fuelled ongoing ...efforts to exploit the tumour microenvironment (TME) for therapy, but strategies aimed at deconstructing the surrounding desmoplastic stroma and targeting the immunosuppressive pathways have largely failed. In fact, evidence has now shown that the stroma is multi-faceted, which illustrates the complexity of exploring features of the TME as isolated targets. In this Review, we describe ways in which the PDAC microenvironment has been targeted and note the current understanding of the clinical outcomes that have unexpectedly contradicted preclinical observations. We also consider the more sophisticated therapeutic strategies under active investigation - multi-modal treatment approaches and exploitation of biologically integrated targets - which aim to remodel the TME against PDAC.
CD44, a non-kinase transmembrane glycoprotein, is overexpressed in several cell types including cancer stem cells and frequently shows alternative spliced variants that are thought to play a role in ...cancer development and progression. Hyaluronan, the main ligand for CD44, binds to and activates CD44 resulting in activation of cell signaling pathways that induces cell proliferation, increases cell survival, modulates cytoskeletal changes, and enhances cellular motility. The different functional roles of CD44 standard (CD44s) and specific CD44 variant (CD44v) isoforms are not fully understood. CD44v contain additional peptide motifs that can interact with and sequester growth factors and cytokines at the cell surface thereby functioning as coreceptors to facilitate cell signaling. Moreover, CD44v were expressed in metastasized tumors, whereas switching between CD44v and CD44s may play a role in regulating epithelial to mesenchymal transition (EMT) and in the adaptive plasticity of cancer cells. Here, we review current data on the structural and functional properties of CD44, the known roles for CD44 in tumorigencity, the regulation of CD44 expression, and the potential for targeting CD44 for cancer therapy.
The antitumor activity of different ent-kaurane diterpenes has been extensively studied. Several investigations have demonstrated the excellent antitumor activity of synthetic derivatives of the ...diterpene atractyligenin. In this research, a series of new synthetic amides and their 15,19-di-oxo analogues obtained from atractyligenin by modifying the C-2, C-15, and C-19 positions were designed in order to dispose of a set of derivatives with different substitutions at the amidic nitrogen. Using different concentrations of the obtained compounds (10–300 μM) a reduction in cell viability of HCT116 colon cancer cells was observed at 48 h of treatment. All the di-oxidized compounds were more effective than their alcoholic precursors. The di-oxidized compounds had already reduced the viability of two colon cancer cells (HCT116 and Caco-2) at 24 h when used at low doses (2.5–15 μM), while they turned out to be poorly effective in differentiated Caco-2 cells, a model of polarized enterocytes. The data reported here provide evidence that di-oxidized compounds induced apoptotic cell death, as demonstrated by the appearance of condensed and fragmented DNA in treated cells, as well as the activation of caspase-3 and fragmentation of its target PARP-1.
A series of Cr-MOF and CoPc (denoted as Cr-MOF@CoPc) nanohybrids were prepared and studied as novel platforms of impedimetric cytosensors for determining living colorectal cancer (CT26) cells using ...electrochemical techniques and by cell imaging. Electrochemical impedance spectroscopy and differential pulse voltammetry results showed extremely low detection limits of 36 and 8 cells mL−1, respectively, within the wide linear concentration range of the CT26 cell suspension (50–1×107 cells mL−1).
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•Cr-MOF and CoPc nanohybrids; novel platforms of cytosensors; the detection of living (CT26) cells.•Ultra-low detection limit 36 and 8 cells mL−1; EIS or DPV; 50–1 × 107 cells mL−1.•High selectivity; good stability; and acceptable reproducibility.
In this study, we have prepared the series of nanohybrids of Cr-based metal-organic framework (Cr-MOF) and cobalt phthalocyanine (CoPc) nanoparticles (denoted as Cr-MOF@CoPc) and investigated them as novel platforms of electrochemical cytosensors for determining colorectal cancer (CT26) cells. The developed Cr-MOF@CoPc nanohybrids were composed of irregularly small nanoparticles, mixed metal valence states of Cr2+/Cr3+/Cr5+ and Co2+/Co3+, rich functional groups of C–O and COO and strong fluorescence performance, as well as high specific area and large pore volume. These intrinsic features of Cr-MOF@CoPc nanohybrids endowed them with strong immobilization ability toward aptamer strands via π- π* stacking, electrostatic interaction, and van der Waals force, excellent electrochemical property, strong fluorescence intensity, and good biocompatibility. Compared with cytosensors based on the sole metal MOFs (Cr-MOF and CoPc) and other reported bulk MOF-based sensors, the constructed Cr-MOF@CoPc-based cytosensor exhibited low detection limit toward CT26 cells, for which the sensing performance was modulated by changing the dosage of CoPc nanoparticles. Electrochemical impedance spectroscopy and differential pulse voltammetry results showed extremely low detection limits of 36 and 8 cells mL−1, respectively, within the concentration range of the CT26 cell suspension (50–1 × 107 cells mL−1), along with high selectivity, excellent stability, and acceptable reproducibility. Thus, the prepared cytosensor can be extensively applied for the analysis of other kinds of cancer cells when anchored their corresponding aptamer strands, providing great potential applications in the biosensor and biomedical fields.
Exosomes, small-membrane vesicles, are secreted by cells and include several types of proteins and nucleic acids. Exosomes transfer cellular information derived from donor cells and are involved in ...various physiological and pathological events, such as organ-specific metastasis. Elucidating the exosome uptake mechanisms is important for understanding the progression processes of organ-specific metastasis. However, whether the exosomes secreted by the donor cells are selectively or non-selectively incorporated into the recipient cells is unknown.
In this study, three human carcinoma cell lines, A549 (lung), HCT116 and COLO205 (colon), were used. The exosome isolation efficiency was compared between three methods: ultracentrifugation, ExoQuick-TC and Total Exosome Isolation kits. Recipient cells were treated with Pitstop 2, an inhibitor of clathrin-dependent endocytosis, or genistein, an inhibitor of caveolae-dependent endocytosis, and then incubated with DiO-labeled exosomes.
Among the three methods examined, ultracentrifugation was the most efficient and reproducible. Exosomes derived from a donor cell line are incorporated into the three cell lines, but the exosome uptake capability was different depending on the recipient cell type and did not depend on the donor cell type. Exosome uptake in COLO205 was inhibited by Pitstop 2 and genistein. Exosome uptake in HCT116 was inhibited by Pitstop 2, but not genistein, while that in A549 cells was not inhibited by these inhibitors. Taken together, these results suggest that the exosomes secreted by donor cells are non-selectively incorporated into recipient cells and that the exosome uptake mechanism is different depending on the recipient cells.
Different recipient cells' exosome uptake capabilities may be involved in organ-specific metastasis.
Background: This study has mainly focused on finding pharmacological effects of ginsenosides that can reduce the unwanted side effects of the cytotoxic anticancer drugs and are highly effective on ...prostate cancer, colorectal cancer, liver cancer, hormone-dependent breast cancer, triple-negative breast cancer, and brain cancer (neuroblastoma). Methods: Minor and rare ginsenosides (GS) of Rh2 which have a high absorption ability and excellent pharmacological actions were treated with the 6 different types of cancer cell lines and their anticancer activities were investigated by analyzing gene expressions associated with various cancers through qPCR and other relevant methods. Results: In cancer cells exposed to Rh2, cell viability and cell migration were reduced, and apoptosis was induced. Each cancer cell was divided into three groups according to the cell proliferation response by Rh2; 1) A group in which the cell viability decreases inversely to an increase in Rh2 treatment concentration; 2) A group in which the cell viability rapidly decreases in Rh2 treatment above a certain level of concentration; 3) A group in which the cell viability was not suppressed below 20-30% even with 100 μL of Rh2, the highest concentration used in this study. Conclusions: It was shown that Rh2 has a significant effect on inhibiting the proliferation of prostate cancer cells and hormone-dependent breast cancer cells.
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