scholarly journals The Aquaporin-3-Inhibiting Potential of Polyoxotungstates

2020 ◽  
Vol 21 (7) ◽  
pp. 2467 ◽  
Author(s):  
Catarina Pimpão ◽  
Inês V. da Silva ◽  
Andreia F. Mósca ◽  
Jacinta O. Pinho ◽  
Maria Manuela Gaspar ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Growth ◽  
Anticancer Drugs ◽  
Inhibitory Concentration ◽  
Yeast Cells ◽  
Anticancer Activities ◽  
Cancer Cell Growth ◽  
Aquaporin 3 ◽  
Anticancer Properties ◽  
First Time

Polyoxometalates (POMs) are of increasing interest due to their proven anticancer activities. Aquaporins (AQPs) were found to be overexpressed in tumors bringing particular attention to their inhibitors as anticancer drugs. Herein, we report for the first time the ability of polyoxotungstates (POTs), such as of Wells–Dawson P2W18, P2W12, and P2W15, and Preyssler P5W30 structures, to affect aquaporin-3 (AQP3) activity and impair melanoma cell migration. The tested POTs were revealed to inhibit AQP3 function with different effects, with P2W18, P2W12, and P5W30 being the most potent (50% inhibitory concentration (IC50) = 0.8, 2.8, and 3.2 µM), and P2W15 being the weakest (IC50 > 100 µM). The selectivity of P2W18 toward AQP3 was confirmed in yeast cells transformed with human aquaglyceroporins. The effect of P2W12 and P2W18 on melanoma cells that highly express AQP3 revealed an impairment of cell migration between 55% and 65% after 24 h, indicating that the anticancer properties of these compounds may in part be due to the blockage of AQP3-mediated permeability. Altogether, our data revealed that P2W18 strongly affects AQP3 activity and cancer cell growth, unveiling its potential as an anticancer drug against tumors where AQP3 is highly expressed.

Human 3α-hydroxysteroid dehydrogenase type 3: structural clues of 5α-DHT reverse binding and enzyme down-regulation decreasing MCF7 cell growth

2016 ◽  
Vol 473 (8) ◽  
pp. 1037-1046 ◽  
Author(s):  
Bo Zhang ◽  
Xiao-Jian Hu ◽  
Xiao-Qiang Wang ◽  
Jean-François Thériault ◽  
Dao-Wei Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Crystal Structure ◽  
Cell Growth ◽  
Mcf7 Cell ◽  
Hydroxysteroid Dehydrogenase ◽  
Cancer Cell Growth ◽  
Down Regulation ◽  
Breast Cancer Cell Growth ◽  
Type 3 ◽  
First Time

Human 3α-HSD3 (3α-hydroxysteroid dehydrogenase type 3) plays an essential role in the inactivation of the most potent androgen 5α-DHT (5α-dihydrotestosterone). The present study attempts to obtain the important structure of 3α-HSD3 in complex with 5α-DHT and to investigate the role of 3α-HSD3 in breast cancer cells. We report the crystal structure of human 3α-HSD3·NADP+·A-dione (5α-androstane-3,17-dione)/epi-ADT (epiandrosterone) complex, which was obtained by co-crystallization with 5α-DHT in the presence of NADP+. Although 5α-DHT was introduced during the crystallization, oxidoreduction of 5α-DHT occurred. The locations of A-dione and epi-ADT were identified in the steroid-binding sites of two 3α-HSD3 molecules per crystal asymmetric unit. An overlay showed that A-dione and epi-ADT were oriented upside-down and flipped relative to each other, providing structural clues for 5α-DHT reverse binding in the enzyme with the generation of different products. Moreover, we report the crystal structure of the 3α-HSD3·NADP+·4-dione (4-androstene-3,17-dione) complex. When a specific siRNA (100 nM) was used to suppress 3α-HSD3 expression without interfering with 3α-HSD4, which shares a highly homologous active site, the 5α-DHT concentration increased, whereas MCF7 cell growth was suppressed. The present study provides structural clues for 5α-DHT reverse binding within 3α-HSD3, and demonstrates for the first time that down-regulation of 3α-HSD3 decreases MCF7 breast cancer cell growth.

scholarly journals Improved Anticancer Activities of a New Pentafluorothio-Substituted Vorinostat-Type Histone Deacetylase Inhibitor

2021 ◽  
Vol 14 (12) ◽  
pp. 1319
Author(s):  
Nils Goehringer ◽  
Yayi Peng ◽  
Bianca Nitzsche ◽  
Hannah Biermann ◽  
Rohan Pradhan ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Histone Deacetylases ◽  
Parent Compound ◽  
Hdac Inhibitors ◽  
Drug Candidate ◽  
Anticancer Activities ◽  
Drug Candidates ◽  
Anticancer Properties ◽  
Ic50 Values ◽  
Potent Drug

The development of new anticancer drugs is necessary in order deal with the disease and with the drawbacks of currently applied drugs. Epigenetic dysregulations are a central hallmark of cancerogenesis and histone deacetylases (HDACs) emerged as promising anticancer targets. HDAC inhibitors are promising epigenetic anticancer drugs and new HDAC inhibitors are sought for in order to obtain potent drug candidates. The new HDAC inhibitor SF5-SAHA was synthesized and analyzed for its anticancer properties. The new compound SF5-SAHA showed strong inhibition of tumor cell growth with IC50 values similar to or lower than that of the clinically applied reference compound vorinostat/SAHA (suberoylanilide hydroxamic acid). Target specific HDAC inhibition was demonstrated by Western blot analyses. Unspecific cytotoxic effects were not observed in LDH-release measurements. Pro-apoptotic formation of reactive oxygen species (ROS) and caspase-3 activity induction in prostate carcinoma and hepatocellular carcinoma cell lines DU145 and Hep-G2 seem to be further aspects of the mode of action. Antiangiogenic activity of SF5-SAHA was observed on chorioallantoic membranes of fertilized chicken eggs (CAM assay). The presence of the pentafluorothio-substituent of SF5-SAHA increased the antiproliferative effects in both solid tumor and leukemia/lymphoma cell models when compared with its parent compound vorinostat. Based on this preliminary study, SF5-SAHA has the prerequisites to be further developed as a new HDAC inhibitory anticancer drug candidate.

scholarly journals Anticancer activities of cyclohexenone derivatives

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Soon Young Shin ◽  
Jihyun Park ◽  
Yearam Jung ◽  
Young Han Lee ◽  
Dongsoo Koh ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cell ◽  
Binding Mode ◽  
Anticancer Activities ◽  
Cancer Cell Growth ◽  
Term Survival ◽  
In Silico Docking ◽  
Cyclohexenone Derivatives

AbstractWe designed 21 ethyl 3,5-diphenyl-2-cyclohexenone-6-carboxylate derivatives to identify compounds exhibiting anticancer activity. To measure the inhibitory effects of the compounds on cancer cell growth, a long-term survival clonogenic assay was performed. Since compounds containing a cyclohexenone moiety inhibit the enzyme acetylcholinesterase, an in vitro acetylcholinesterase assay was performed for all 21 cyclohexenone derivatives. To examine the effect of the derivative that exhibited the best cancer cell growth inhibition on the induction of apoptosis by demonstrating the activation of caspases and apoptosis regulatory proteins, immunoblotting and immunofluorescence microscopic analyses were performed. The binding mode between the cyclohexenone derivatives and acetylcholinesterase was elucidated at the molecular level using in silico docking. Druggability was evaluated based on ligand efficiency.

scholarly journals Ellagic Acid and Schisandrins: Natural Biaryl Polyphenols with Therapeutic Potential to Overcome Multidrug Resistance in Cancer

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 458
Author(s):  
Sabesan Yoganathan ◽  
Anushan Alagaratnam ◽  
Nikita Acharekar ◽  
Jing Kong
Keyword(s):  
Multidrug Resistance ◽  
Small Molecules ◽  
Anticancer Drugs ◽  
Abc Transporters ◽  
Ellagic Acid ◽  
Therapeutic Potential ◽  
Anticancer Activities ◽  
Glycoprotein P ◽  
Major Mechanism ◽  
Anticancer Properties

Multidrug resistance (MDR) is one of the major clinical challenges in cancer treatment and compromises the effectiveness of conventional anticancer chemotherapeutics. Among known mechanisms of drug resistance, drug efflux via ATP binding cassette (ABC) transporters, namely P-glycoprotein (P-gp) has been characterized as a major mechanism of MDR. The primary function of ABC transporters is to regulate the transport of endogenous and exogenous small molecules across the membrane barrier in various tissues. P-gp and similar efflux pumps are associated with MDR because of their overexpression in many cancer types. One of the intensively studied approaches to overcome this mode of MDR involves development of small molecules to modulate P-gp activity. This strategy improves the sensitivity of cancer cells to anticancer drugs that are otherwise ineffective. Although multiple generations of P-gp inhibitors have been identified to date, reported compounds have demonstrated low clinical efficacy and adverse effects. More recently, natural polyphenols have emerged as a promising class of compounds to address P-gp linked MDR. This review highlights the chemical structure and anticancer activities of selected members of a structurally unique class of ‘biaryl’ polyphenols. The discussion focuses on the anticancer properties of ellagic acid, ellagic acid derivatives, and schisandrins. Research reports regarding their inherent anticancer activities and their ability to sensitize MDR cell lines towards conventional anticancer drugs are highlighted here. Additionally, a brief discussion about the axial chirality (i.e., atropisomerism) that may be introduced into these natural products for medicinal chemistry studies is also provided.

scholarly journals Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survival

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Qiang Liu ◽  
Hongliang Shen ◽  
Andrew Naguib ◽  
Robert M. Weiss ◽  
Darryl T. Martin
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cell Growth ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Cancer Cell Growth

AbstractProstate cancer is the most common solid organ malignancy in the United States, and has the highest probability of all cancers in becoming invasive. New molecular targets are needed to define and impede the growth and progression of advanced prostate cancers. Claudins (Cldns) are transmembrane proteins that regulate paracellular permeability and cell polarity, and their levels are elevated in many human cancers such as breast, ovarian, pancreatic, and prostatic cancers. Previously, we found that Cldn3 and Cldn4 are expressed in aggressive high-grade human prostate cancer specimens. We and others have shown that there are higher levels of Cldn3 and Cldn4 in metastatic human prostate cancer cells than in normal human prostate cells. The result of targeting Cldn3 and Cldn4 expression on the growth and viability of prostate cancer cells has not been elucidated. Human prostate cancer PC3 and LNCaP cells were transfected with Cldn3 or -4 small interfering RNAs (siRNAs). Cldn3/Cldn4 siRNA treatment resulted in a greater than 85% decrease in the protein levels of Cldn3 and Cldn4, which was accompanied by a 30–40% decrease in prostate cancer cell growth and a 60–65% reduction in cell viability. There was decreased cell migration with Cldn3 and Cldn4 siRNA in both PC3 and LNCaP cells and a 60–75% decrease in the number of clones when treated with siCldn3 or siCldn4 compared to control. Knocking down Cldn3/Cldn4 affects prostate cancer cell growth and survival and may have therapeutic implications.

scholarly journals Gallnuts: A Potential Treasure in Anticancer Drug Discovery

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jiayu Gao ◽  
Xiao Yang ◽  
Weiping Yin ◽  
Ming Li
Keyword(s):  
Anticancer Drugs ◽  
Case Reports ◽  
Bioactive Metabolites ◽  
Anticancer Activities ◽  
Web Based ◽  
Scientific Databases ◽  
Anticancer Properties ◽  
Rhus Chinensis ◽  
Pharmacological Studies ◽  
Fundamental Understanding

Introduction. In the discovery of more potent and selective anticancer drugs, the research continually expands and explores new bioactive metabolites coming from different natural sources. Gallnuts are a group of very special natural products formed through parasitic interaction between plants and insects. Though it has been traditionally used as a source of drugs for the treatment of cancerous diseases in traditional and folk medicinal systems through centuries, the anticancer properties of gallnuts are barely systematically reviewed. Objective. To evidence the traditional uses and phytochemicals and pharmacological mechanisms in anticancer aspects of gallnuts, a literature review was performed. Materials and Methods. The systematic review approach consisted of searching web-based scientific databases including PubMed, Web of Science, and Science Direct. The keywords for searching include gallnut, Galla Chinensis, Rhus chinensis, Rhus potaninii, Rhus punjabensis, nutgall, gall oak, Quercus infectoria, Quercus lusitanica, and galla turcica. Two reviewers extracted papers independently to remove the papers unrelated to the anticancer properties of gallnuts. Patents, abstracts, case reports, and abstracts in symposium and congress were excluded. Results and Conclusion. As a result, 14 articles were eligible to be evaluated. It is primarily evident that gallnuts contain a number of bioactive metabolites, which account for anticancer activities. The phytochemical and pharmacological studies reviewed strongly underpin a fundamental understanding of anticancer properties for gallnuts (Galla Chinensis and Galla Turcica) and support their ongoing clinical uses in China. The further bioactive compounds screening and evaluation, pharmacological investigation, and clinical trials are expected to progress gallnut-based development to finally transform the wild medicinal gallnuts to the valuable authorized anticancer drugs.

scholarly journals A Review of the Structure–Activity Relationship of Natural and Synthetic Antimetastatic Compounds

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 138 ◽  
Author(s):  
Liew ◽  
Malagobadan ◽  
Arshad ◽  
Nagoor
Keyword(s):  
Cell Growth ◽  
Functional Groups ◽  
Natural Compound ◽  
Anticancer Activities ◽  
Cancer Cell Growth ◽  
Anticancer Compounds ◽  
Structural Modifications ◽  
Structure Activity ◽  
Relationship Of ◽  
Trifluoromethyl Groups

There are innumerable anticancer compounds derived from either natural or synthetic origins. Many of these compounds have been further developed through structural modifications to not only inhibit cancer cell growth but also to exert an antimetastatic effect. This is achieved by attaching different substituents to generate different structure–activity relationships. This review highlights the effectiveness of different functional groups known to have antimigration and antiproliferation activities, such as fluoro, methoxy, methyl, amino, hydroxy, nitro, bromo, chloro, methylamino, ethoxy, carbonyl, iodo, and trifluoromethyl groups. Additionally, the positioning of these functional groups plays an important role in their anticancer activities, which was evident in one of our studies comparing analogues of a natural compound. Thus, this review suggests future recommendations for the design and development of improved anticancer drugs with higher efficacy.

scholarly journals Natural Phytochemicals in Bladder Cancer Prevention and Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Yong Xia ◽  
Ruijiao Chen ◽  
Guangzhen Lu ◽  
Changlin Li ◽  
Sen Lian ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Anticancer Drugs ◽  
Anticancer Activities ◽  
First Line ◽  
Anticancer Properties ◽  
Bladder Cancer Cells ◽  
Cancer Types ◽  
Available Information ◽  
New Anticancer Drugs

Phytochemicals are natural small-molecule compounds derived from plants that have attracted attention for their anticancer activities. Some phytochemicals have been developed as first-line anticancer drugs, such as paclitaxel and vincristine. In addition, several phytochemicals show good tumor suppression functions in various cancer types. Bladder cancer is a malignant tumor of the urinary system. To date, few specific phytochemicals have been used for bladder cancer therapy, although many have been studied in bladder cancer cells and mouse models. Therefore, it is important to collate and summarize the available information on the role of phytochemicals in the prevention and treatment of bladder cancer. In this review, we summarize the effects of several phytochemicals including flavonoids, steroids, nitrogen compounds, and aromatic substances with anticancer properties and classify the mechanism of action of phytochemicals in bladder cancer. This review will contribute to facilitating the development of new anticancer drugs and strategies for the treatment of bladder cancer using phytochemicals.

794: Valproic Acid Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo

2006 ◽  
Vol 175 (4S) ◽  
pp. 257-257
Author(s):  
Jennifer Sung ◽  
Qinghua Xia ◽  
Wasim Chowdhury ◽  
Shabana Shabbeer ◽  
Michael Carducci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Valproic Acid ◽  
Cell Growth ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Growth
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