A viable strategy for screening the effects of glycan heterogeneity on target organ adhesion and biodistribution in live mice

2018 ◽  
Vol 54 (63) ◽  
pp. 8693-8696 ◽  
Author(s):  
Akihiro Ogura ◽  
Sayaka Urano ◽  
Tsuyoshi Tahara ◽  
Satoshi Nozaki ◽  
Regina Sibgatullina ◽  
...  

Screening a diverse set of heterogeneous glycoalbumins for binding to several cancer cell types in cell- and mouse-based assays.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
V. S. Christina ◽  
R. Lakshmi Sundaram ◽  
V. Sivamurugan ◽  
D. Thirumal Kumar ◽  
C. D. Mohanapriya ◽  
...  

AbstractMatrix metalloproteinases (MMPs) are pivotal for cancer cell migration and metastasis which are generally over-expressed in such cell types. Many drugs targeting MMPs do so by binding to the conserved catalytic domains and thus exhibit poor selectivity due to domain-similarities with other proteases. We report herein the binding of a novel compound [3-(E-3,4-dihydroxycinnamaoyloxyl)-2-hydroxypropyl 9Z, 12Z-octadeca-9, 12-dienoate; Mol. wt: 516.67 Da], (C1), isolated from a seagrass, Cymodocea serrulata to the unconserved hemopexin-like (PEX) domain of MMP2 (− 9.258 kcal/mol). MD simulations for 25 ns, suggest stable ligand-target binding. In addition, C1 killed an ovarian cancer cell line, PA1 at IC50: 5.8 μM (lesser than Doxorubicin: 8.6 µM) and formed micronuclei, apoptotic bodies and nucleoplasmic bridges whilst causing DNA laddering, S and G2/M phase dual arrests and MMP disturbance, suggesting intrinsic apoptosis. The molecule increased mRNA transcripts of BAX and BAD and down-regulated cell survival genes, Bcl-xL, Bcl-2, MMP2 and MMP9. The chemical and structural details of C1 were deduced through FT-IR, GC–MS, ESI–MS, 1H and 13C NMR [both 1D and 2D] spectra.



2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Daiki Terada ◽  
Fumihiro Kawai ◽  
Hiroki Noguchi ◽  
Satoru Unzai ◽  
Imtiaj Hasan ◽  
...  


2021 ◽  
Vol 22 (18) ◽  
pp. 10098
Author(s):  
Francesca Paradiso ◽  
Stefano Serpelloni ◽  
Lewis W. Francis ◽  
Francesca Taraballi

From the development of self-aggregating, scaffold-free multicellular spheroids to the inclusion of scaffold systems, 3D models have progressively increased in complexity to better mimic native tissues. The inclusion of a third dimension in cancer models allows researchers to zoom out from a significant but limited cancer cell research approach to a wider investigation of the tumor microenvironment. This model can include multiple cell types and many elements from the extracellular matrix (ECM), which provides mechanical support for the tissue, mediates cell-microenvironment interactions, and plays a key role in cancer cell invasion. Both biochemical and biophysical signals from the extracellular space strongly influence cell fate, the epigenetic landscape, and gene expression. Specifically, a detailed mechanistic understanding of tumor cell-ECM interactions, especially during cancer invasion, is lacking. In this review, we focus on the latest achievements in the study of ECM biomechanics and mechanosensing in cancer on 3D scaffold-based and scaffold-free models, focusing on each platform’s level of complexity, up-to-date mechanical tests performed, limitations, and potential for further improvements.



2008 ◽  
Vol 92 (2) ◽  
pp. 221-222 ◽  
Author(s):  
A. E. Tanner ◽  
K. E. Saker ◽  
Y. Ju ◽  
Y. W. Lee ◽  
S. O’Keefe ◽  
...  


2018 ◽  
Vol 4 (5) ◽  
pp. 1622-1629 ◽  
Author(s):  
Jekaterina Kazantseva ◽  
Roman Ivanov ◽  
Michael Gasik ◽  
Toomas Neuman ◽  
Irina Hussainova


2019 ◽  
Vol 116 (3) ◽  
pp. 375a-376a
Author(s):  
Sangwoo Kwon ◽  
Se Jik Han ◽  
Kyung Sook Kim


2019 ◽  
Vol 27 (5) ◽  
pp. 1569-1587 ◽  
Author(s):  
Jing Zhang ◽  
Yu Yang ◽  
Shen’ao Zhou ◽  
Xueyan He ◽  
Xuan Cao ◽  
...  

Abstract Microtubule-targeting agents (MTAs) are a class of most widely used chemotherapeutics and their mechanism of action has long been assumed to be mitotic arrest of rapidly dividing tumor cells. In contrast to such notion, here we show—in many cancer cell types—MTAs function by triggering membrane TNF (memTNF)-mediated cancer-cell-to-cancer-cell killing, which differs greatly from other non-MTA cell-cycle-arresting agents. The killing is through programmed cell death (PCD), either in way of necroptosis when RIP3 kinase is expressed, or of apoptosis in its absence. Mechanistically, MTAs induce memTNF transcription via the JNK-cJun signaling pathway. With respect to chemotherapy regimens, our results establish that memTNF-mediated killing is significantly augmented by IAP antagonists (Smac mimetics) in a broad spectrum of cancer types, and with their effects most prominently manifested in patient-derived xenograft (PDX) models in which cell–cell contacts are highly reminiscent of human tumors. Therefore, our finding indicates that memTNF can serve as a marker for patient responsiveness, and Smac mimetics will be effective adjuvants for MTA chemotherapeutics. The present study reframes our fundamental biochemical understanding of how MTAs take advantage of the natural tight contact of tumor cells and utilize memTNF-mediated death signaling to induce the entire tumor regression.



Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 293 ◽  
Author(s):  
Sónia Teixeira ◽  
Miguel M. Santos ◽  
Maria H. Fernandes ◽  
João Costa-Rodrigues ◽  
Luís C. Branco

Herein the quantitative synthesis of eight new mono- and dianionic Organic Salts and Ionic Liquids (OSILs) from alendronic acid (ALN) is reported by following two distinct sustainable and straightforward methodologies, according to the type of cation. The prepared ALN-OSILs were characterized by spectroscopic techniques and their solubility in water and biological fluids was determined. An evaluation of the toxicity towards human healthy cells and also human breast, lung and bone (osteosarcoma) cell lines was performed. Globally, it was observed that the monoanionic OSILs showed lower toxicity than the corresponding dianionic structures to all cell types. The highest cytotoxic effect was observed in OSILs containing a [C2OHMIM] cation, in particular [C2OHMIM][ALN]. The latter showed an improvement in IC50 values of ca. three orders of magnitude for the lung and bone cancer cell lines as well as fibroblasts in comparison with ALN. The development of OSILs with high cytotoxicity effect towards the tested cancer cell types, and containing an anti-resorbing molecule such as ALN may represent a promising strategy for the development of new pharmacological tools to be used in those pathological conditions.



2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Matthew Tegowski ◽  
Cheng Fan ◽  
Albert S. Baldwin

AbstractSeveral recent publications demonstrated that DRD2-targeting antipsychotics such as thioridazine induce proliferation arrest and apoptosis in diverse cancer cell types including those derived from brain, lung, colon, and breast. While most studies show that 10–20 µM thioridazine leads to reduced proliferation or increased apoptosis, here we show that lower doses of thioridazine (1–2 µM) target the self-renewal of basal-like breast cancer cells, but not breast cancer cells of other subtypes. We also show that all breast cancer cell lines tested express DRD2 mRNA and protein, regardless of thioridazine sensitivity. Further, DRD2 stimulation with quinpirole, a DRD2 agonist, promotes self-renewal, even in cell lines in which thioridazine does not inhibit self-renewal. This suggests that DRD2 is capable of promoting self-renewal in these cell lines, but that it is not active. Further, we show that dopamine can be detected in human and mouse breast tumor samples. This observation suggests that dopamine receptors may be activated in breast cancers, and is the first time to our knowledge that dopamine has been directly detected in human breast tumors, which could inform future investigation into DRD2 as a therapeutic target for breast cancer.



2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Claudia Torricelli ◽  
Sara Salvadori ◽  
Giuseppe Valacchi ◽  
Karel Souček ◽  
Eva Slabáková ◽  
...  

Since the ability of cancer cells to evade apoptosis often limits the efficacy of radiotherapy and chemotherapy, autophagy is emerging as an alternative target to promote cell death. Therefore, we wondered whether Rottlerin, a natural polyphenolic compound with antiproliferative effects in several cell types, can induce cell death in MCF-7 breast cancer cells. The MCF-7 cell line is a good model of chemo/radio resistance, being both apoptosis and autophagy resistant, due to deletion of caspase 3 gene, high expression of the antiapoptotic protein Bcl-2, and low expression of the autophagic Beclin-1 protein. The contribution of autophagy and apoptosis to the cytotoxic effects of Rottlerin was examined by light, fluorescence, and electron microscopic examination and by western blotting analysis of apoptotic and autophagic markers. By comparing caspases-3-deficient (MCF-73def) and caspases-3-transfected MCF-7 cells (MCF-73trans), we found that Rottlerin induced a noncanonical, Bcl-2-, Beclin 1-, Akt-, and ERK-independent autophagic death in the former- and the caspases-mediated apoptosis in the latter, in not starved conditions and in the absence of any other treatment. These findings suggest that Rottlerin could be cytotoxic for different cancer cell types, both apoptosis competent and apoptosis resistant.



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