scholarly journals Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer Cells

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 282
Author(s):  
Neelu Batra ◽  
Anhao Sam ◽  
Tibebe Woldemariam ◽  
George Talbott ◽  
Ralph W. de Vere White ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biological Activities ◽  
Altered Expression ◽  
Growth And Survival ◽  
Androgen Synthesis ◽  
Level Of Activity ◽  
Low Toxicity ◽  
Hplc Fractionation ◽  
High Bioavailability ◽  
Combined Data

Our group and others have previously shown that genistein combined polysaccharide (GCP), an aglycone isoflavone-rich extract with high bioavailability and low toxicity, can inhibit prostate cancer (CaP) cell growth and survival as well as androgen receptor (AR) activity. We now elucidate the mechanism by which this may occur using LNCaP and PC-346C CaP cell lines; GCP can inhibit intracrine androgen synthesis in CaP cells. UPLC-MS/MS and qPCR analyses demonstrated that GCP can mediate a ~3-fold decrease in testosterone levels (p < 0.001) and cause decreased expression of intracrine androgen synthesis pathway enzymes (~2.5-fold decrease of 3βHSD (p < 0.001), 17βHSD (p < 0.001), CYP17A (p < 0.01), SRB1 (p < 0.0001), and StAR (p < 0.01)), respectively. Reverse-phase HPLC fractionation and bioassay identified three active GCP fractions. Subsequent NMR and LC-MS analysis of the fraction with the highest level of activity, fraction 40, identified genistein as the primary active component of GCP responsible for its anti-proliferative, pro-apoptotic, and anti-AR activity. GCP, fraction 40, and genistein all mediated at least a ~2-fold change in these biological activities relative to vehicle control (p < 0.001). Genistein caused similar decreases in the expression of 17βHSD and CYP17A (2.5-fold (p < 0.001) and 1.5-fold decrease (p < 0.01), respectively) compared to GCP, however it did not cause altered expression of the other intracrine androgen synthesis pathway enzymes; 3βHSD, SRB1, and StAR. Our combined data indicate that GCP and/or genistein may have clinical utility and that further pre-clinical studies are warranted.

scholarly journals The Effects of Selenium Nanoparticles (SeNPs) on Ruminant

2020 ◽  
pp. 1-8
Author(s):  
Khandsuren Badgar ◽  
József Prokisch
Keyword(s):  
Antioxidant Defense ◽  
Biological Activities ◽  
Essential Element ◽  
Selenium Nanoparticles ◽  
Food Supplementation ◽  
Physiological Processes ◽  
Ruminant Animals ◽  
Low Toxicity ◽  
High Bioavailability

This study examines the role of selenium and the effects of selenium nanoparticle-enriched food supplementation especially in ruminant animals. Selenium is an essential element that has multiple biological activities. Particularly it is important for many physiological processes, especially for the functions of reproductive and immune systems, metabolism of thyroid hormones, as well as antioxidant defense. Also, the presence of selenium nanoparticles in the diet provide a high content of selenium in milk and meat due to its high bioavailability and low toxicity, which is essential for humans.

Click Reactions in Chemistry of Triterpenes - Advances Towards Development of Potential Therapeutics

2018 ◽  
Vol 25 (5) ◽  
pp. 636-658 ◽  
Author(s):  
Jan Pokorny ◽  
Lucie Borkova ◽  
Milan Urban
Keyword(s):  
Biological Activities ◽  
Synthetic Approach ◽  
Clinical Use ◽  
New Approach ◽  
Click Reactions ◽  
Drug Candidates ◽  
The Past ◽  
Low Toxicity ◽  
New Compounds ◽  
Potential Therapeutics

Triterpenoids are natural compounds with a large variety of biological activities such as anticancer, antiviral, antibacterial, antifungal, antiparazitic, antiinflammatory and others. Despite their low toxicity and simple availability from the natural resources, their clinical use is still severely limited by their higher IC50 and worse pharmacological properties than in the currently used therapeutics. This fact encouraged a number of researchers to develop new terpenic derivatives more suitable for the potential clinical use. This review summarizes a new approach to improve both, the activity and ADME-Tox properties by connecting active terpenes to another modifying molecules using click reactions. Within the past few years, this synthetic approach was well explored yielding a lot of great improvements of the parent compounds along with some less successful attempts. A large quantity of the new compounds presented here are superior in both activity and ADME-Tox properties to their parents. This review should serve the researchers who need to promote their hit triterpenic structures towards their clinical use and it is intended as a guide for the chemical synthesis of better drug candidates.

scholarly journals Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial Activity

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 542
Author(s):  
Gustavo Penteado Battesini Carretero ◽  
Greice Kelle Viegas Saraiva ◽  
Magali Aparecida Rodrigues ◽  
Sumika Kiyota ◽  
Marcelo Porto Bemquerer ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Biological Activities ◽  
Biological Effects ◽  
Membrane Surface ◽  
Helical Structure ◽  
Helical Conformation ◽  
Property A ◽  
Cellular Processes ◽  
Double Stranded Dna ◽  
Low Toxicity

In a large variety of organisms, antimicrobial peptides (AMPs) are primary defenses against pathogens. BP100 (KKLFKKILKYL-NH2), a short, synthetic, cationic AMP, is active against bacteria and displays low toxicity towards eukaryotic cells. BP100 acquires a α-helical conformation upon interaction with membranes and increases membrane permeability. Despite the volume of information available, the action mechanism of BP100, the selectivity of its biological effects, and possible applications are far from consensual. Our group synthesized a fluorescent BP100 analogue containing naphthalimide linked to its N-terminal end, NAPHT-BP100 (Naphthalimide-AAKKLFKKILKYL-NH2). The fluorescence properties of naphthalimides, especially their spectral sensitivity to microenvironment changes, are well established, and their biological activities against transformed cells and bacteria are known. Naphthalimide derived compounds are known to interact with DNA disturbing related processes as replication and transcription, and used as anticancer agents due to this property. A wide variety of techniques were used to demonstrate that NAPHT-BP100 bound to and permeabilized zwitterionic POPC and negatively charged POPC:POPG liposomes and, upon interaction, acquired a α-helical structure. Membrane surface high peptide/lipid ratios triggered complete permeabilization of the liposomes in a detergent-like manner. Membrane disruption was driven by charge neutralization, lipid aggregation, and bilayer destabilization. NAPHT-BP100 also interacted with double-stranded DNA, indicating that this peptide could also affect other cellular processes besides causing membrane destabilization. NAPHT-BP100 showed increased antibacterial and hemolytic activities, compared to BP100, and may constitute an efficient antimicrobial agent for dermatological use. By conjugating BP100 and naphthalimide DNA binding properties, NAPHT-BP100 bound to a large extent to the bacterial membrane and could more efficiently destabilize it. We also speculate that peptide could enter the bacteria cell and interact with its DNA in the cytoplasm.

scholarly journals Herb-target virtual screening and network pharmacology for prediction of molecular mechanism of Danggui Beimu Kushen Wan for prostate cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hong Li ◽  
Andrew Hung ◽  
Angela Wei Hong Yang
Keyword(s):  
Prostate Cancer ◽  
Binding Affinity ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Tight Binding ◽  
Experimental Studies ◽  
Network Pharmacology ◽  
High Morbidity ◽  
High Binding ◽  
High Binding Affinity

AbstractProstate cancer (PCa) is a cancer that occurs in the prostate with high morbidity and mortality. Danggui Beimu Kushen Wan (DBKW) is a classic formula for patients with difficult urination including PCa. This study aimed to investigate the molecular mechanisms of DBKW for PCa. We obtained DBKW compounds from our previous reviews. We identified potential targets for PCa from literature search, currently approved drugs and Open Targets database and filtered them by protein–protein interaction network analysis. We selected 26 targets to predict three cancer-related pathways. A total of 621 compounds were screened via molecular docking using PyRx and AutoDock Vina against 21 targets for PCa, producing 13041 docking results. The binding patterns and positions showed that a relatively small number of tight-binding compounds from DBKW were predicted to interact strongly and selectively with three targets. The top five high-binding-affinity compounds were selected to generate a network, indicating that compounds from all three herbs had high binding affinity against the 21 targets and may have potential biological activities with the targets. DBKW contains multi-targeting agents that could act on more than one pathway of PCa simultaneously. Further studies could focus on validating the computational results via experimental studies.

scholarly journals Regulation of mRNA Translation by Hormone Receptors in Breast and Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3254
Author(s):  
Jianling Xie ◽  
Eric P. Kusnadi ◽  
Luc Furic ◽  
Luke A. Selth
Keyword(s):  
Prostate Cancer ◽  
Protein Synthesis ◽  
Causes Of Death ◽  
Hormone Receptors ◽  
Mrna Translation ◽  
Estrogen Receptor Α ◽  
Growth And Survival ◽  
Cancer Types ◽  
Breast And Prostate Cancer ◽  
Hormone Signalling

Breast and prostate cancer are the second and third leading causes of death amongst all cancer types, respectively. Pathogenesis of these malignancies is characterised by dysregulation of sex hormone signalling pathways, mediated by the estrogen receptor-α (ER) in breast cancer and androgen receptor (AR) in prostate cancer. ER and AR are transcription factors whose aberrant function drives oncogenic transcriptional programs to promote cancer growth and progression. While ER/AR are known to stimulate cell growth and survival by modulating gene transcription, emerging findings indicate that their effects in neoplasia are also mediated by dysregulation of protein synthesis (i.e., mRNA translation). This suggests that ER/AR can coordinately perturb both transcriptional and translational programs, resulting in the establishment of proteomes that promote malignancy. In this review, we will discuss relatively understudied aspects of ER and AR activity in regulating protein synthesis as well as the potential of targeting mRNA translation in breast and prostate cancer.

Altered expression of genes regulating angiogenesis in experimental androgen-independent prostate cancer

The Prostate ◽  
2007 ◽  
Vol 68 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Heléne Gustavsson ◽  
Karin Jennbacken ◽  
Karin Welén ◽  
Jan-Erik Damber
Keyword(s):  
Prostate Cancer ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Androgen Independent

Inhibición de Crecimiento de Tumores de Cáncer de Próstata en Hipertermia Magnética mediada por Nanopartículas en Estudios Preclínicos: una Revisión de Alcance

2021 ◽  
Author(s):  
◽  
J. A. Parada Peralta
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Magnetic Nanoparticle ◽  
Magnetic Hyperthermia ◽  
Tumor Growth Inhibition ◽  
Tissue Penetration ◽  
Deep Tissue ◽  
Incidence And Mortality ◽  
Low Toxicity ◽  
The Relationship

Prostate Cancer is one of the major concern types of cancer among men with respect to incidence and mortality. One relatively recent therapy against it, provided by Nanomedicine, is Nanoparticle mediated Magnetic Hyperthermia, which consists on tumor heating when exposed to an Alternating Magnetic Field in order to inhibit tumor growth (around 42 °C) (and make tumor sensible to other therapies: synergia) or to cause cancer cell apoptosis (greater temperature than 42°C). This procedure has several advantages like deep-tissue-penetration, targeted heating, low toxicity by Nanoparticles, and others. To this treatment, some of the Magnetic Nanoparticle properties are fundamental to its success, principaly the size, morphology, etc. Here, therefore, the relationship between the size of the employed Nanoparticles and the Tumor Growth Inhibition that cause is reviewed when treating Prostate Cancer tumors on mice models by Magnetic Hyperthermia.

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