An Efficient Method for the Isolation of Toxins from Pteridium aquilinum and Evaluation of Ptaquiloside Against Cancer and Non-cancer Cells

Planta Medica ◽  
2021 ◽  
Author(s):  
Courtney Williams ◽  
Simon J. Allison ◽  
Roger M. Phillips ◽  
Peter A. Linley ◽  
Colin W. Wright

AbstractThe common fern, bracken (Pteridium aquilinum), is well known for its toxic effects on livestock due principally to the carcinogenic constituent ptaquiloside (1), although other toxins are present including the cyanogenic glycoside, prunasin (2). Here, we report an improved and relatively “green” process for the isolation of 1 and 2 from fresh bracken fronds and the evaluation of 1 for cytotoxicity against several cancer cell lines. The results indicate that 1 displays selective toxicity against cancer cells relative to noncancer retinal epithelial cells, and the improved method for the isolation of 1 is expected to facilitate further exploration of its pharmacological properties.

2019 ◽  
Vol 19 (16) ◽  
pp. 1298-1368 ◽  
Author(s):  
Ankit Jain ◽  
Poonam Piplani

: Triazole is a valuable platform in medicinal chemistry, possessing assorted pharmacological properties, which could play a major role in the common mechanisms associated with various disorders like cancer, infections, inflammation, convulsions, oxidative stress and neurodegeneration. Structural modification of this scaffold could be helpful in the generation of new therapeutically useful agents. Although research endeavors are moving towards the growth of synthetic analogs of triazole, there is still a lot of scope to achieve drug discovery break-through in this area. Upcoming therapeutic prospective of this moiety has captured the attention of medicinal chemists to synthesize novel triazole derivatives. The authors amalgamated the chemistry, synthetic strategies and detailed pharmacological activities of the triazole nucleus in the present review. Information regarding the marketed triazole derivatives has also been incorporated. The objective of the review is to provide insights to designing and synthesizing novel triazole derivatives with advanced and unexplored pharmacological implications.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 858
Author(s):  
Kyriaki-Marina Lyra ◽  
Archontia Kaminari ◽  
Katerina N. Panagiotaki ◽  
Konstantinos Spyrou ◽  
Sergios Papageorgiou ◽  
...  

An efficient doxorubicin (DOX) drug delivery system with specificity against tumor cells was developed, based on multi-walled carbon nanotubes (MWCNTs) functionalized with guanidinylated dendritic molecular transporters. Acid-treated MWCNTs (oxCNTs) interacted both electrostatically and through hydrogen bonding and van der Waals attraction forces with guanidinylated derivatives of 5000 and 25,000 Da molecular weight hyperbranched polyethyleneimine (GPEI5K and GPEI25K). Chemical characterization of these GPEI-functionalized oxCNTs revealed successful decoration with GPEIs all over the oxCNTs sidewalls, which, due to the presence of guanidinium groups, gave them aqueous compatibility and, thus, exceptional colloidal stability. These GPEI-functionalized CNTs were subsequently loaded with DOX for selective anticancer activity, yielding systems of high DOX loading, up to 99.5% encapsulation efficiency, while the DOX-loaded systems exhibited pH-triggered release and higher therapeutic efficacy compared to that of free DOX. Most importantly, the oxCNTs@GPEI5K-DOX system caused high and selective toxicity against cancer cells in a non-apoptotic, fast and catastrophic manner that cancer cells cannot recover from. Therefore, the oxCNTs@GPEI5K nanocarrier was found to be a potent and efficient nanoscale DOX delivery system, exhibiting high selectivity against cancerous cells, thus constituting a promising candidate for cancer therapy.


2021 ◽  
Vol 9 (7) ◽  
pp. 687
Author(s):  
Harsha Prakash ◽  
Shiori Motobe ◽  
Takahiro Nagasawa ◽  
Tomonori Somamoto ◽  
Miki Nakao

Fish mucosal surface is a significant interface for pathogens to infect from an aqueous environment. In addition to mucosal innate and adaptive immune factors, epithelial cells are considered as a significant physical barrier against microbial invasion. Previously, we identified a mammalian CD46-like complement regulatory protein (Tecrem) in teleost and detected its expression on epithelial cells derived from fin, suggesting its physiological role on the fish surface. This study examines the homeostatic roles of Tecrem in maintaining the fish epithelium, by analyzing the expression behavior of Tecrem on the fin-derived epithelial cell lines (KF-1 from the common carp and CFS from ginbuna crucian carp) using monoclonal and polyclonal anti-Tecrem antibodies. Expression of KF-1 protein was associated with the adhesion of KF-1, and the adhesion was enhanced by anti-Tecrem treatments of the cells. Stimulation of the epithelial cells with anti-Tecrem enhanced wound healing, protein expression of tight-junction proteins, and cell density of the KF-1 and CFS monolayer culture. These results suggest that Tecrem on epithelial cells play a homeostatic role in maintaining intactness of the surface epithelial barrier, implying that modification of Tecrem expression may develop a novel tool to improve the first-line defense against pathogens in aquaculture.


Proceedings ◽  
2020 ◽  
Vol 78 (1) ◽  
pp. 17
Author(s):  
Maria Mantzari ◽  
Foteini Gartziou ◽  
Eleni Lambrou ◽  
Spyridon Mourtas ◽  
Paraskevi Zagana ◽  
...  

Arsonoliposomes (ARSL) constitute a particular class of liposomes that incorporate arsonolipids (ARS) into their membranes. ARSL realize selective toxicity to cancer cells; thus, they are an important tool in the treatment of cancer. Folic acid (FA) is widely used in targeted drug delivery due to its high affinity for the folate receptors that are overexpressed in cancer cell membranes. The aim of our studies was to develop novel triple-negative breast cancer (TNBC)-targeted ARSL by incorporating folic acid-conjugated polyethylene-glycol PEG-lipid (FA-PEG-lipid) into their membrane and loading them with anticancer drug doxorubicin (DOX). ARSL incorporating 0.1 mol% of FA-PEG-lipid were prepared and loaded with DOX, using the active loading protocol. They were characterized for their size distribution, zeta potential and drug entrapment efficiency (%). Their cytotoxic activity towards TNBC cell lines, particularly MDA-MB-231 (epithelial human breast cancer cells) and MCF7 (human breast cancer cells), was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT-assay. The first results demonstrated enhanced toxicity of this novel type of ARSL towards cancer cells, which is particularly interesting and deserves further exploitation.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1079
Author(s):  
Manuela Zangrossi ◽  
Patrizia Romani ◽  
Probir Chakravarty ◽  
Colin D.H. Ratcliffe ◽  
Steven Hooper ◽  
...  

Late relapse of disseminated cancer cells is a common feature of breast and prostate tumors. Several intrinsic and extrinsic factors have been shown to affect quiescence and reawakening of disseminated dormant cancer cells (DDCCs); however, the signals and processes sustaining the survival of DDCCs in a foreign environment are still poorly understood. We have recently shown that crosstalk with lung epithelial cells promotes survival of DDCCs of estrogen receptor-positive (ER+) breast tumors. By using a lung organotypic system and in vivo dissemination assays, here we show that the TFEB-lysosomal axis is activated in DDCCs and that it is modulated by the pro-survival ephrin receptor EphB6. TFEB lysosomal direct targets are enriched in DDCCs in vivo and correlate with relapse in ER+ breast cancer patients. Direct coculture of DDCCs with alveolar type I-like lung epithelial cells and dissemination in the lung drive lysosomal accumulation and EphB6 induction. EphB6 contributes to survival, TFEB transcriptional activity, and lysosome formation in DDCCs in vitro and in vivo. Furthermore, signaling from EphB6 promotes the proliferation of surrounding lung parenchymal cells in vivo. Our data provide evidence that EphB6 is a key factor in the crosstalk between disseminated dormant cancer cells and the lung parenchyma and that the TFEB-lysosomal pathway plays an important role in the persistence of DDCCs.


2015 ◽  
Vol 2 (1) ◽  
pp. 1
Author(s):  
Christopher G. Hill ◽  
John F. McDonald

The molecular basis of cancer is not merely the consequence of structural and/or regulatory mutations in genes, but additionally to disruptions in networks of regulatory interactions existing among these genes and other components of the genome. Disruptions in network relationships may manifest as the loss, gain or reversal of functionally significant interactive gene relationships in cancer cells. In this study, we first employ an unsupervised (Pearson correlation) approach to quantitatively estimate the overall change in network relationships between precursor (control) ovarian surface epithelial cells and ovarian cancer epithelial cells. We find that ovarian cancer cells display a significant overall reduction in correlated gene network interactions relative to normal precursor cells reflective of an overall loss of regulatory control.  We next focus on gene relationships that qualitatively change between normal and cancer samples. We find that biological processes significantly over represented among differentially expressed genes are substantially different from those associated with genes involved in qualitatively disrupted network interactions. Our findings provide novel insights into the processes underlying ovarian cancer and identify a potential new class of genes for targeted therapy.


1992 ◽  
Vol 2 (2) ◽  
pp. 77-84 ◽  
Author(s):  
Alexander Marx ◽  
Mary Osborn ◽  
Socrates Tzartos ◽  
Kerstin I. Geuder ◽  
Berthold Schalke ◽  
...  

The coincidence of autoantibodies against the acetylcholine receptor (AChR) and muscle striational antigens (SA) is a characteristic finding in thymoma-associated myasthenia gravis (MG), but their origins are still unresolved. Some common muscle antigens that were shown to be targets of anti-SA autoantibodies in thymoma-associated MG have also been detected in normal or neoplastic thymic epithelial cells, suggesting that the release of (eventually altered) antigens from the thymic tumors could elicit SA autoimmunity. In contrast to this model, we report here that titin, which is a recently reported target of SA autoimmunity, is not expressed in thymomas. In addition, we show that skeletal muscle type-II fibers exhibit a striational immunoreactivity with monoclonal antibody mAb155, which was previously identified to label a very immunogenic cytoplasmic epitope of the AChR and neoplastic epithelial cells of MGassociated thymomas. We conclude from these findings that titin autoimmunity in thymoma-associated MG is either due to a molecular mimicry mechanism involving tumor antigens (other than titin) or is a secondary phenomenon following release of titin from muscle. Based on the common immunoreactivity of the AChR, a striational antigen and thymoma, we suggest as the pathogenetic mechanism of thymoma-associated MGa "circulus vitiosus" in which SA autoimmunity could help maintain the AChR autoimmunity that is primarily elicited by the thymomas.


1996 ◽  
Vol 24 (2) ◽  
pp. 240-248 ◽  
Author(s):  
Herbert Dardik ◽  
Fred Silvestri ◽  
Teresa Alasio ◽  
Silvia Berry ◽  
Mark Kahn ◽  
...  

1997 ◽  
Vol 272 (5) ◽  
pp. G1201-G1208 ◽  
Author(s):  
A. C. Stevens ◽  
J. Matthews ◽  
P. Andres ◽  
V. Baffis ◽  
X. X. Zheng ◽  
...  

Interleukin-15 (IL-15) shares many biological functions with interleukin-2 (IL-2) due to common receptor components. IL-15 binds to the IL-2 receptor (IL-2R) beta-chain and the common gamma-chain receptor in addition to one other IL-15 binding receptor protein (IL-15R alpha). Both IL-2R beta- and gamma-chains are required to promote cell growth in hematopoietic cells. The colonic cryptlike epithelial cell line T84 contains the common gamma-chain but lacks the IL-2R beta-chain. We report IL-15R alpha-chain mRNA in T84 cells with the use of reverse transcriptase-polymerase chain reaction. T84 and normal colonic epithelial cells bind a FLAG-IL-15 fusion protein in immunoperoxidase and flow cytometric experiments. In addition, IL-15, but not IL-2, accelerates and enhances the development of transepithelial resistance across T84 monolayers in a dose-dependent fashion. We conclude that normal and T84 colonic epithelial cells express IL-15R alpha and are able to bind IL-15. IL-15 can deliver a nonproliferative functional signal in the absence of IL-2R beta-chain in T84 cells.


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