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2022 ◽  
Vol 12 (5) ◽  
pp. 1053-1058
Author(s):  
Shunfu Zhu ◽  
Neng Jiang ◽  
Jianjun Zhu

Objective: Yes-associated protein 1 (YAP1) regulates cell proliferation and apoptosis. Abnormal miR-375 level was related to thyroid cancer. Software predicted a relationship between miR-375 and YAP1. Our study investigated whether miR-375 regulates YAP1 expression and affects thyroid cancer cells. Methods: The tumor tissues and adjacent tissues of thyroid cancer patients were collected to measure miR-375 and YAP1 expression. The dual luciferase reporter experiment verified the regulation between miR-375 and YAP1. Thyroid cancer cell line B-CPAP and TPC-1 cells were divided into miR-NC group and miR-375 mimic group followed by analysis of cell proliferation by flow cytometry, caspase-3 activity, and cell clone formation ability by plate cloning assay. Results: Compared with adjacent cancer tissues, miR-375 in thyroid cancer tissues was decreased and YAP1 was increased. miR-375 targets YAP1. Compared with Nthy-ori 3-1 cells, miR-375 in B-CPAP and TPC-1 cells was significantly reduced and YAP1 was increased. Transfection with miR-375 mimic significantly inhibited cell proliferation, increase caspase-3 activity, and reduced the ability of cells to form clones. Conclusion: miR-375 can inhibit YAP1 expression, decrease the proliferation of thyroid cancer cells, induce cell apoptosis, and reduce clone formation.


2022 ◽  
Vol 9 ◽  
Author(s):  
Ponnusamy Packialakshmi ◽  
Perumal Gobinath ◽  
Daoud Ali ◽  
Saud Alarifi ◽  
Raman Gurusamy ◽  
...  

In this work, we synthesize the sulfonated Schiff bases of the chitosan derivatives 2a-2j without the use of a catalyst in two moderately straightforward steps with good yield within a short reaction time. The morphology and chemical structure of chitosan derivatives were investigated using FT-IR, NMR (1H—13C), XRD, and SEM. Furthermore, our chitosan derivatives were tested for their anticancer activity against the MCF-7 cancer cell line, and doxorubicin was used as a standard. In addition, the normal cell lines of the breast cancer cell MCF-10A, and of the lung cell MRC-5 were tested. Compound 2 h, with a GI50 value of 0.02 µM for MCF-7, is highly active compared with the standard doxorubicin and other compounds. The synthesized compounds 2a-2j exhibit low cytotoxicity, with IC50 > 100 μg/ml, against normal cell lines MCF-10A, MRC-5. We also provide the results of an in-silico study involving the Methoxsalen protein (1Z11). Compound 2h exhibits a higher binding affinity for 1Z11 protein (−5.9 kcal/mol) and a lower binding affinity for Doxorubicin (−5.3 kcal/mol) than certain other compounds. As a result of the aforementioned findings, the use of compound 2h has an anticancer drug will be researched in the future.


2022 ◽  
Vol 4 (1) ◽  
Author(s):  
Paul Prasse ◽  
Pascal Iversen ◽  
Matthias Lienhard ◽  
Kristina Thedinga ◽  
Chris Bauer ◽  
...  

ABSTRACT Computational drug sensitivity models have the potential to improve therapeutic outcomes by identifying targeted drug components that are likely to achieve the highest efficacy for a cancer cell line at hand at a therapeutic dose. State of the art drug sensitivity models use regression techniques to predict the inhibitory concentration of a drug for a tumor cell line. This regression objective is not directly aligned with either of these principal goals of drug sensitivity models: We argue that drug sensitivity modeling should be seen as a ranking problem with an optimization criterion that quantifies a drug’s inhibitory capacity for the cancer cell line at hand relative to its toxicity for healthy cells. We derive an extension to the well-established drug sensitivity regression model PaccMann that employs a ranking loss and focuses on the ratio of inhibitory concentration and therapeutic dosage range. We find that the ranking extension significantly enhances the model’s capability to identify the most effective anticancer drugs for unseen tumor cell profiles based in on in-vitro data.


Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 483
Author(s):  
Sofia Zazouli ◽  
Mohammed Chigr ◽  
Patrícia A. B. Ramos ◽  
Daniela Rosa ◽  
Maria M. Castro ◽  
...  

Zizyphus lotus L. is a perennial shrub particularly used in Algerian folk medicine, but little is known concerning the lipophilic compounds in the most frequently used parts, namely, root bark, pulp, leaves and seeds, which are associated with health benefits. In this vein, the lipophilic fractions of these morphological parts of Z. lotus from Morocco were studied by gas chromatography–mass spectrometry (GC–MS), and their antiproliferative and antimicrobial activities were evaluated. GC–MS analysis allowed the identification and quantification of 99 lipophilic compounds, including fatty acids, long-chain aliphatic alcohols, pentacyclic triterpenic compounds, sterols, monoglycerides, aromatic compounds and other minor components. Lipophilic extracts of pulp, leaves and seeds were revealed to be mainly composed of fatty acids, representing 54.3–88.6% of the total compounds detected. The leaves and seeds were particularly rich in unsaturated fatty acids, namely, (9Z,12Z)-octadeca-9,12-dienoic acid (2431 mg kg−1 of dry weight) and (9Z)-octadec-9-enoic acid (6255 mg kg−1 of dry weight). In contrast, root bark contained a high content of pentacyclic triterpenic compounds, particularly betulinic acid, accounting for 9838 mg kg−1 of dry weight. Root bark extract showed promising antiproliferative activity against a triple-negative breast cancer cell line, MDA-MB-231, with a half-maximal inhibitory concentration (IC50) = 4.23 ± 0.18 µg mL−1 of extract. Leaf extract displayed interesting antimicrobial activity against Escherichia coli, methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermis, presenting minimum inhibitory concentration (MIC) values from 1024 to 2048 µg mL−1 of extract. Our results demonstrate that Zizyphus lotus L. is a source of promising bioactive components, which can be exploited as natural ingredients in pharmaceutical formulations.


Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 117
Author(s):  
Marcel Hrubša ◽  
Raúl Alva ◽  
Mst Shamima Parvin ◽  
Kateřina Macáková ◽  
Jana Karlíčková ◽  
...  

Flavonoids are associated with positive cardiovascular effects. However, due to their low bioavailability, metabolites are likely responsible for these properties. Recently, one of these metabolites, 4-methylcatechol, was described to be a very potent antiplatelet compound. This study aimed to compare its activity with its 22 close derivatives both of natural or synthetic origin in order to elucidate a potential structure–antiplatelet activity relationship. Blood from human volunteers was induced to aggregate by arachidonic acid (AA), collagen or thrombin, and plasma coagulation was also studied. Potential toxicity was tested on human erythrocytes as well as on a cancer cell line. Our results indicated that 17 out of the 22 compounds were very active at a concentration of 40 μM and, importantly, seven of them had an IC50 on AA-triggered aggregation below 3 μM. The effects of the most active compounds were confirmed on collagen-triggered aggregation too. None of the tested compounds was toxic toward erythrocytes at 50 μM and four compounds partly inhibited proliferation of breast cancer cell line at 100 μM but not at 10 μM. Additionally, none of the compounds had a significant effect on blood coagulation or thrombin-triggered aggregation. This study hence reports four phenol derivatives (4-ethylcatechol, 4-fluorocatechol, 2-methoxy-4-ethylphenol and 3-methylcatechol) suitable for future in vivo testing.


2022 ◽  
Author(s):  
Alina Batzilla ◽  
Junyan Lu ◽  
Jarno Kivioja ◽  
Kerstin Putzker ◽  
Joe Lewis ◽  
...  

The development of cancer therapies may be improved by the discovery of tumor-specific molecular dependencies. The requisite tools include genetic and chemical perturbations, each with its strengths and limitations. Drug perturbations can be readily applied to primary cancer samples at a large scale, but mechanistic understanding of hits and further pharmaceutical development is often complicated by the fact that a small compound has a range of affinities to multiple proteins. To computationally infer the molecular dependencies of individual cancers from their ex-vivo drug sensitivity profiles, we developed a mathematical model that deconvolutes these data using measurements of protein-drug affinity profiles. Our method, DepInfeR, correctly identified known dependencies, including EGFR dependence in Her2+ breast cancer cell line, FLT3 dependence in AML tumors with FLT3-ITD mutations, and the differential dependencies on the B-cell receptor pathway in two major subtypes of chronic lymphocytic leukemia (CLL). Furthermore, our method uncovered new subgroup-specific dependencies, including a previously unreported dependence of high-risk CLL on Checkpoint kinase 1 (CHEK1). The method also produced a more accurate map of the molecular dependencies in a heterogeneous set of 117 CLL samples. The ability to deconvolute polypharmacological phenotypes into underlying causal molecular dependencies should increase the utility of high-throughput drug response assays for functional precision oncology.


2022 ◽  
Author(s):  
Ruixia Bai ◽  
Wanying Song ◽  
Yan Cui ◽  
Haining Gao ◽  
Yuxing Zhao ◽  
...  

Abstract ObjectiveTo explore the autophagy effect of ghrelin on the ovarian cancer cell line SK-OV-3. And the lncRNA which regulate the ghrelin effect SK-OV-3 autophagy was showed.Methodsthe expression of ghrelin in the ovarian cancer tissues was analyzed according GEPIA database and HPA database. The CCK-8 was used to detect the the optimal concentration of ghrelin effect on the SK-OV-3. The influence on the SK-OV-3 cell autophagy by ghrelin was showed by detecting the expression of Beclin-1, LC3Ⅰand LC3Ⅱusing western blot. Linc00598 selected as the effecting the SK-OV-3 cells autophagy by ghrelin using RNA-Seq. And the Linc00598 which was silenced or overexressed promote the SK-OV-3 cells autophagy treated by ghrelin though western blot.ResultsGhrelin was expressed low in the ovarian cancer tissues. Ghrelin concentratio of 600 ng/ml was the optimal concentration o and 24 h was the optimal time. Ghrelin can promote the SK-OV-3 cell autophagy. Ghrelin mainly through linc00598 to promote the SK-OV-3 cells autophagy. When the linc00598 silenced, ghrelin promote SK-OV-3 cells autophagy was inhibited. And When the linc00598 overexpressed, ghrelin promote SK-OV-3 cells autophagy was inhanced.ConclusionsGhrelin promote SK-OV-3 cells autophagy. Additionally, we proved that ghrelin regulated the progression of SK-OV-3 cells autophagy by linc00598/ Beclin1 axis.


Plants ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 194
Author(s):  
Ciprian Nicolae Pilut ◽  
Aniko Manea ◽  
Ioana Macasoi ◽  
Amadeus Dobrescu ◽  
Doina Georgescu ◽  
...  

In the field of oncology, the plant kingdom has an inexhaustible supply of bioactive compounds. Phytochemical compounds isolated from Helleborus species have been found to be useful in various chronic diseases. This has brought Helleborus to the attention of medical researchers. H. purpurascens is a plant characteristic of the Carpathian area, known since ancient times for its beneficial effects. The aim of the study was to evaluate the flavonoids composition of a hydroalcoholic extract of H. purpurascens, as well as to assess its antioxidant activity and antitumor potential at the level of two healthy cell lines and four tumor cell lines. In addition, the expression of the genes involved in the apoptotic process (Bcl-2, Bad, and Bax) were evaluated. The results indicated that the extract has a high concentration of flavonoids, such as epicatechin, quercetin, and kaempferol. The extract has an increased antioxidant activity, very similar to that of the standard, ascorbic acid and cytotoxic effects predominantly in the breast cancer cell line, being free of cytotoxic effects in healthy cell lines. Underlying the cytotoxic effect is the induction of the process of apoptosis, which in the present study was highlighted by decreasing the expression of anti-apoptotic genes (Bcl-2) and increasing the expression of pro-apoptotic genes (Bad and Bax). In conclusion, the hydroalcoholic extract of H. purpurascens can be considered an important source for future medical applications in cancer therapy.


Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 169
Author(s):  
Javier Pérez Quiñones ◽  
Cornelia Roschger ◽  
Aitziber Iturmendi ◽  
Helena Henke ◽  
Andreas Zierer ◽  
...  

The design and study of efficient polymer-based drug delivery systems for the controlled release of anticancer drugs is one of the pillars of nanomedicine. The fight against metastatic and invasive cancers demands therapeutic candidates with increased and selective toxicity towards malignant cells, long-term activity and reduced side effects. In this sense, polyphosphazene nanocarriers were synthesized for the sustained release of the anticancer drugs camptothecin (CPT) and epirubicin (EPI). Linear poly(dichloro)phosphazene was modified with lipophilic tocopherol or testosterone glycinate, with antioxidant and antitumor activity, and with hydrophilic Jeffamine M1000 to obtain different polyphosphazene nanocarriers. It allowed us to encapsulate the lipophilic CPT and the more hydrophilic EPI. The encapsulation process was carried out via solvent exchange/precipitation, attaining a 9.2–13.6 wt% of CPT and 0.3–2.4 wt% of EPI. CPT-loaded polyphosphazenes formed 140–200 nm aggregates in simulated body physiological conditions (PBS, pH 7.4), resulting in an 80–100-fold increase of CPT solubility. EPI-loaded polyphosphazenes formed 250 nm aggregates in an aqueous medium. CPT and EPI release (PBS, pH 7.4, 37 °C) was monitored for 202 h, being almost linear during the first 8 h. The slow release of testosterone and tocopherol was also sustained for 150 hours in PBS (pH 7.4 and 6.0) at 37 °C. The co-delivery of testosterone or tocopherol and the anticancer drugs from the nanocarriers was expected. Cells of the human breast cancer cell line MCF-7 demonstrated good uptake of anticancer-drug-loaded nanocarriers after 6 hours. Similarly, MCF-7 spheroids showed good uptake of the anticancer-drug-loaded aggregates after 72 hours. Almost all anticancer-drug-loaded polyphosphazenes exhibited similar or superior toxicity against MCF-7 cells and spheroids when compared to raw anticancer drugs. Additionally, cell-cycle arrest in the G2/M phase was increased in response to the drug-loaded nanocarriers. Almost no toxicity of anticancer-drug-loaded aggregates against primary human lung fibroblasts was observed. Furthermore, the aggregates displayed no hemolytic activity, which is in contrast to the parent anticancer drugs. Consequently, synthesized polyphosphazene-based nanocarriers might be potential nanomedicines for chemotherapy.


2022 ◽  
Author(s):  
Nidhi chaudhary ◽  
Manish Pratap Singh ◽  
Preeti Sirohi ◽  
Shadma Afzal ◽  
Nand K. Singh

Abstract ObjectiveIn the present study, we green synthesized ZnO NPs (zinc oxide nanoparticles) from Senna occidentalis leaf extract which were subsequently assessed for their cytotoxic and antioxidant activity on colon cancer SW480 cell line.Results Zinc oxide nanoparticles were characterized by using UV-Vis spectroscopy, X-ray diffractometer (XRD), Particle size analyzer (PSA), Fourier transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (FE-SEM), Energy-dispersive X-ray (EDS) and atomic force microscope (AFM) analysis. The PSA, XRD and AFM showed 20-50 nm size and nearly cuboidal and irregular shaped of the ZnO NPs. The synthesized ZnO nanoparticles were evaluated for their anticancer activity on human colon cancer cell line (SW480) by using MTT and neutral red uptake assay. The SW480 colon cancer cells were treated with various concentrations of ZnO NPs in the range of 20–100 µg/ml for 2 hrs. The result showed that ZnO NPs could reduce cell viability of SW480 cells up to 50% at the concentration of 100 µg/ml and induce membrane leakage in a concentration dependent manner.ConclusionThe anticancer activity of zinc oxide nanoparticles has showed that these can be used as effective anti-cancer agent against colon cancer cell lines (SW480).


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