Search Results (35)

Inflammation, oxidative stress, and androgen activity are key features in benign prostate hyperplasia (BPH). Risks associated with the long-term use of 5α-reductase inhibitors have led to the search for alternative therapies, including food supplements. This study investigates the effectiveness of the combination of pollen extracts, namely Graminex^®G96^® (G) and Teupol 25P (T), towards oxidative stress and inflammation on human macrophages and benign prostate hyperplasia cells (BPH-1), both of which are LPS stimulated. The Nrf2-dependent antioxidant intracellular cascade as well as the NF-ĸB-driven inflammatory cascades were analyzed. The anti-proliferative effect of G and T, alone and in association, were evaluated on prostatic adenocarcinoma cells (PC-3) and BPH-1 cells. Finally, the inhibitory activity of GT on 5α-reductase was investigated in PC-3 cells by measuring epiandrosterone amounts, with the 5α-reductase inhibitor finasteride administered for comparison. All experiments were conducted in triplicate; data are presented as mean values ± standard deviations. Statistical analysis was performed using one-way analysis of variance. Our work demonstrates that GT promotes Nrf2-dependent antioxidant responses and counteracts the NF-ĸB-driven pathway in macrophages. GT is effective in counteracting the expression of pro-inflammatory cytokines and the generation of reactive oxygen species by promoting HO-1-dependent antioxidant responses in BPH-1 cells. GT reduces PC-3 and BPH-1 proliferation when associated with finasteride through a statistically significant inhibition of 5α-reductase activity. Data obtained in vitro and in silico demonstrate the potential efficacy of a multitargeted approach in the treatment of BPH. Full article

Secondary metabolites such as flavonoids bring a range of biological properties to natural products, making them potential candidates for the pharmaceutical industry. Piptadenia stipulacea (Benth.) Ducke is well known in Brazil as Jurema Branca, and yet few studies have investigated its biological and phytochemical properties. This study aimed to characterize and evaluate the biological properties of ethanolic extract obtained from the bark of Jurema Branca. Characterization was performed by qualitative phytochemistry, HPLC, and mass spectroscopy. The antibacterial properties were investigated by microdilution method, cytotoxicity by MTT method, biocompatibility testing with human erythrocytes was performed, and antioxidant properties were investigated using DPPH and ABTS radical scavenging. The phytochemical tests demonstrated that rhamnetin and luteolin were the main constituents of the extract. This is the first report of these compounds in this species. The extract presented activity against Staphylococcus aureus (MIC = 500 µg/mL) and demonstrated activity against human colorectal adenocarcinoma (HCT-116), prostate adenocarcinoma (PC-3), and acute myeloid leukemia (HL-60) cell lines with IC₅₀ of 37.96, 37.6, and 27.82 µg/mL, respectively, for this Piptadenia genus. Additionally, the extract presented excellent biocompatibility and antioxidant activity (IC₅₀ = 956.7 and 147.2 µg/mL in DPPH and ABTS methods, respectively). These results are novel for the Piptadenia genus and pave the way for further evaluations regarding the biological importance of this species. Full article

Biologically active compounds of natural origin, such as betulin, are a source of obtaining new medicinal substances. The presence of chemically active hydroxyl groups in the betulin structure at C-3 and C-28 positions enables esterification with dicarboxylic acid anhydrides or carboxylic acids. As a result of a four-step synthesis, difunctional betulin derivatives were obtained, which were evaluated for their antiproliferative activity against the following human cell lines: leukemia (MV4-11), (A549), breast cancer (MCF-7), prostate adenocarcinoma (PC-3), colon cancer (HCT116), pancreatic cancer (MiaPaca-2), and melanoma (Hs294T). The target 3-carboxyacyl-28-alkynyloyl betulin derivatives showed significant antiproliferative activity against MV4-11 cells. For 3-carboxyacylbetulins and their selected alkynyl derivatives, studies to investigate the effect on the cell cycle and apoptosis process, as well as drug similarity analysis, were performed. Full article

Platycarpha glomerata (Thunb.) Less. has recently become a plant species of interest to researchers due to its biological activities and less toxic effects. Therefore, the aim of the study is to evaluate the in vitro anticancer potential and phytochemical constituents of P. glomerata plant extracts. Phytochemical screening and FTIR were carried out using standard methods. The antioxidant activity was accessed by determining its ability to scavenge the DPPH radical and nitric oxide radical, whereas the anticancer activity against prostate (DU-145 and PC-3), human T-lymphocyte (SKU-T), gastric adenocarcinoma (AGS), and human prostatic epithelial (PNTA1) cell line was evaluated using the MTT assay. The phytochemical analysis revealed the presence of tannins, flavonoids, saponins, steroids, terpenoids, and cardiac glycosides. The FTIR spectrum for the aqueous extract displayed characteristic peaks for O–H, C=O, C=C, and =C–H stretch. The aqueous ethanol and methanol extracts showed significant dose-dependent DPPH radical scavenging capacity. The aqueous, ethanol, and methanol extracts showed minimum NO scavenging activity of 4.3%, 9.6%, and 11.7% at 2500 µg/mL. The water extract demonstrated good activity against S. aureus, E. coli, and B. pumilus with an MIC of 0.195 mg/mL. The ethanol and methanol extracts significantly reduced the percentage proliferation of DU-145, PC-3, and SKU-T cells at 100 μg/mL. These extracts demonstrated strong dose-dependent DPPH and NO scavenging and antibacterial and cell proliferation inhibition activities. The strong bioactivity of P. glomerata makes it a good candidate for the isolation and identification of active compounds for anticancer and related illnesses. Full article

This study describes a simple, cost-effective, and eco-friendly method for synthesizing silver nanoparticles using a rosmarinic acid extract from Perilla frutescens (PFRAE) as the bioreduction agent. The resulting nanoparticles, called PFRAE-AgNPs, were characterized using various analytical techniques. The UV–Vis spectrum confirmed the formation of PFRAE-AgNPs, and the FTIR spectrum indicated the participation of rosmarinic acid in their synthesis and stabilization. The XRD pattern revealed the crystal structure of PFRAE-AgNPs, and the TEM analysis showed their spherical morphology with sizes ranging between 20 and 80 nm. The DLS analysis indicated that PFRAE-AgNPs were monodispersed with an average diameter of 44.0 ± 3.2 nm, and the high negative zeta potential (−19.65 mV) indicated their high stability. In the antibacterial assays, the PFRAE-AgNPs showed potent activity against both Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial pathogens, suggesting that they could be used as a potential antibacterial agent in the clinical setting. Moreover, the antioxidant activity of PFRAE-AgNPs against DPPH and ABTS radical scavengers highlights their potential in the treatment of various oxidative stress-related diseases. PFRAE-AgNPs also demonstrated significant anticancer activity against a range of cell lines including human colon cancer (COLO205), human prostate carcinoma (PC-3), human lung adenocarcinoma (A549), and human ovarian cancer (SKOV3) cell lines suggesting their potential in cancer therapy. The nanoparticles may also have potential in drug delivery, as their small size and high stability could enable them to cross biological barriers and deliver drugs to specific target sites. In addition to the aforementioned properties, PFRAE-AgNPs were found to be biocompatible towards normal (CHO) cells, which is a crucial characteristic for their application in cancer therapy and drug delivery systems. Their antibacterial, antioxidant, and anticancer properties make them promising candidates for the development of new therapeutic agents. Furthermore, their small size, high stability, and biocompatibility could enable them to be used in drug delivery systems to enhance drug efficacy and reduce side effects. Full article

Human high-mobility group-B (HMGB) proteins regulate gene expression in prostate cancer (PCa), a leading cause of oncological death in men. Their role in aggressive PCa cancers, which do not respond to hormonal treatment, was analyzed. The effects of HMGB1 and HMGB2 silencing upon the expression of genes previously related to PCa were studied in the PCa cell line PC-3 (selected as a small cell neuroendocrine carcinoma, SCNC, PCa model not responding to hormonal treatment). A total of 72% of genes analyzed, using pre-designed primer panels, were affected. HMGB1 behaved mostly as a repressor, but HMGB2 as an activator. Changes in SERPINE1, CDK1, ZWINT, and FN1 expression were validated using qRT-PCR after HMGB1 silencing or overexpression in PC-3 and LNCaP (selected as an adenocarcinoma model of PCa responding to hormonal treatment) cell lines. Similarly, the regulatory role of HMGB2 upon SERPINE1, ZWINT, FN1, IGFPB3, and TYMS expression was validated, finding differences between cell lines. The correlation between the expression of HMGB1, HMGB2, and their targets was analyzed in PCa patient samples and also in PCa subgroups, classified as neuroendocrine positive or negative, in public databases. These results allow a better understanding of the role of HMGB proteins in PCa and contribute to find specific biomarkers for aggressive PCa. Full article

Recent studies have demonstrated the association of APP and Aβ with cancer, suggesting that BACE1 may play an important role in carcinogenesis. In the present study, we assessed BACE1’s usefulness as a therapeutic target in prostate cancer (PCa). BACE1 expression was observed in human PCa tissue samples, patient-derived xenografts (PDX), human PCa xenograft tissue in nude mice, and transgenic adenocarcinoma of the mouse prostate (TRAMP) tissues by immunohistochemistry (IHC) analysis. Additionally, the downstream product of BACE1 activity, i.e., Aβ1-42 expression, was also observed in these PCa tissues by IHC as well as by PET imaging in TRAMP mice. Furthermore, BACE1 gene expression and activity was confirmed in several established PCa cell lines (LNCaP, C4-2B-enzalutamide sensitive [S], C4-2B-enzalutamide resistant [R], 22Rv1-S, 22Rv1-R, PC3, DU145, and TRAMP-C1) by real-time PCR and fluorometric assay, respectively. Treatment with a pharmacological inhibitor of BACE1 (MK-8931) strongly reduced the proliferation of PCa cells in in vitro and in vivo models, analyzed by multiple assays (MTT, clonogenic, and trypan blue exclusion assays and IHC). Cell cycle analyses revealed an increase in the sub-G1 population and a significant modulation in other cell cycle stages (G1/S/G2/M) following MK-8931 treatment. Most importantly, in vivo administration of MK-8931 intraperitoneal (30 mg/kg) strongly inhibited TRAMP-C1 allograft growth in immunocompetent C57BL/6 mice (approximately 81% decrease, p = 0.019). Furthermore, analysis of tumor tissue using the prostate cancer-specific pathway array revealed the alteration of several genes involved in PCa growth and progression including Forkhead O1 (FOXO1). All together, these findings suggest BACE1 as a novel therapeutic target in advanced PCa. Full article

Driven by the growing threat of cancer, many research efforts are directed at developing new chemotherapeutic agents, where the central role is played by transition metal complexes. The proper ligand design serves as a key factor to unlock the anticancer potential of a particular metal center. Following a recent trend, we have prepared unsymmetrical pincer ligands that combine benzothiazole and thiocarbamate donor groups. These compounds are shown to readily undergo direct cyclopalladation, affording the target S,C,N-type Pd(II) pincer complexes both in solution and in the absence of a solvent. The solid-phase strategy provided the complexes in an efficient and ecologically friendly manner. The resulting palladacycles are fully characterized using nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy and, in one case, by single-crystal X-ray diffraction (XRD). The solvent-free reactions are additionally analyzed by powder XRD. The pincer complexes exhibit remarkable cytotoxicity against several solid and blood cancer cell lines, including human colorectal carcinoma (HCT116), breast cancer (MCF7), prostate adenocarcinoma (PC3), chronic myelogenous leukemia (K562), multiple plasmacytoma (AMO1), and acute lymphoblastic leukemia (H9), with the dimethylamino-substituted derivative being particularly effective. The latter also induced an appreciable level of apoptosis in both parental and doxorubicin-resistant cells K562 and K562/iS9, vindicating the high anticancer potential of this type of palladacycles. Full article

The Eph kinases are the largest receptor tyrosine kinases (RTKs) family in humans. PC3 human prostate adenocarcinoma cells are a well-established model for studying Eph–ephrin pharmacology as they naturally express a high level of EphA2, a promising target for new cancer therapies. A pharmacological approach with agonists did not show significant efficacy on tumor growth in prostate orthotopic murine models, but reduced distal metastasis formation. In order to improve the comprehension of the pharmacological targeting of Eph receptors in prostate cancer, in the present work, we investigated the efficacy of Eph antagonism both in vitro and in vivo, using UniPR1331, a small orally bioavailable Eph–ephrin interaction inhibitor. UniPR1331 was able to inhibit PC3 cells’ growth in vitro in a dose-dependent manner, affecting the cell cycle and inducing apoptosis. Moreover, UniPR1331 promoted the PC3 epithelial phenotype, downregulating epithelial mesenchymal transition (EMT) markers. As a consequence, UniPR1331 reduced in vitro PC3 migration, invasion, and vasculomimicry capabilities. The antitumor activity of UniPR1331 was confirmed in vivo when administered alone or in combination with cytotoxic drugs in PC3-xenograft mice. Our results demonstrated that Eph antagonism is a promising strategy for inhibiting prostate cancer growth, especially in combination with cytotoxic drugs. Full article

A phytochemical investigation of the roots of Citrus × paradisi Macfad. (Rutaceae) led to the isolation of two new compounds, namely 1-formyl-5-hydroxy-N-methylindolin-1-ium (1) and decyloxycleomiscosin D (2), along with ten known compounds: 1,1-dimethylpyrrolidin-1-ium-2-carboxylate (3), furan-2,3-diol (4), 5-methoxyseselin (5), umbelliferone (6), scopoletin (7), citracridone I (8), citracridone II (9), citracridone III (10), limonin (11) and lupeol (12). The structures were determined through the comprehensive spectroscopic analysis of 1D and 2D NMR and EI- and ESI-MS, as well as a comparison with the published data. Notably, compounds 3 and 4 from the genus Citrus are reported here for the first time. In addition, the MeOH extract of the roots and compounds 1–7 were screened against the human adenocarcinoma alveolar basal epithelial cell line A549 and the Caucasian prostate adenocarcinoma cell line PC3 using the MTT assay. While the extract showed significant activity, with IC₅₀ values of 35.2 and 38.1 µg/mL, respectively, compounds 1–7 showed weak activity, with IC₅₀ values of 99.2 to 250.2 µM and 99.5 to 192.7 µM, respectively. Full article

Annona glabra L. (AngTE) and Annona squamosa L. (AnsTE) fruits have been widely used in cancer treatment. Accordingly, their extracts were used to synthesize silver nanoparticles via a biogenic route (Ang-AgNPs) and (Ans-AgNPs), respectively. Chemical profiling was established using UPLC-QTOF-MS/MS. All species were tested for anticancer activity against human cervical cancer cells (HeLa), prostate adenocarcinoma metastatic (PC3), and ovary adenocarcinoma (SKOV3) using sulphorhodamine B assay. Apoptosis was determined using Annexin flow cytometry along with cell cycle analysis and supported by a molecular docking. The antibacterial and synergistic effect when combined with gentamicin were evaluated. A total of 114 compounds were tentatively identified, mainly acetogenins and ent-kaurane diterpenes. AnsTE and Ans-AgNPs had the most potent cytotoxicity on HeLa and SKOV3 cells, inducing a significant apoptotic effect against all tumor cells. The AnsTE and Ans-AgNPs significantly arrested PC3, SKOV3, and HeLa cells in the S phase. The nanoparticles demonstrated greater antibacterial and antifungal activities, as well as a synergistic effect with gentamicin against P. aeruginosa and E. coli. Finally, a molecular docking was attempted to investigate the binding mode of the identified compounds in Bcl-2 proteins’ receptor, implying that the fruits and their nanoparticles are excellent candidates for treating skin infections in patients with ovarian or prostatic cancer. Full article

Neglected tropical diseases affect the world’s poorest populations with soil-transmitted helminthiasis and schistosomiasis being among the most prevalent ones. Mass drug administration is currently the most important control measure, but the use of the few available drugs is giving rise to increased resistance of the parasites to the drugs. Different approaches are needed to come up with new therapeutic agents against these helminths. Fungi are a source of secondary metabolites, but most fungi remain largely uninvestigated as anthelmintics. In this report, the anthelmintic activity of Albatrellus confluens against Caenorhabditis elegans was investigated using bio-assay guided isolation. Grifolin (1) and neogrifolin (2) were identified as responsible for the anthelmintic activity. Derivatives 4–6 were synthesized to investigate the effect of varying the prenyl chain length on anthelmintic activity. The isolated compounds 1 and 2 and synthetic derivatives 4–6, as well as their educts 7–10, were tested against Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum. Prenyl-2-orcinol (4) and geranylgeranyl-2-orcinol (6) showed promising activity against newly transformed schistosomula. The compounds 1, 2, 4, 5, and 6 were also screened for antiproliferative or cytotoxic activity against two human cancer lines, viz. prostate adenocarcinoma cells (PC-3) and colorectal adenocarcinoma cells (HT-29). Compound 6 was determined to be the most effective against both cell lines with IC₅₀ values of 16.1 µM in PC-3 prostate cells and 33.7 µM in HT-29 colorectal cells. Full article

Ozoroa insignis Del. is an ethnobotanical plant widely used in traditional medicine for various ailments, including schistosomiasis, tapeworm, and hookworm infections. From the so far not investigated fruits of Ozoroa insignis, the anthelmintic principles could be isolated through bioassay-guided isolation using Caenorhabditis elegans and identified by NMR spectroscopic analysis and mass spectrometric studies. Isolated 6-[8(Z)-pentadecenyl] anacardic (1), 6-[10(Z)-heptadecenyl] anacardic acid (2), and 3-[7(Z)-pentadecenyl] phenol (3) were evaluated against the 5 parasitic organisms Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum, which mainly infect humans and other mammals. Compounds 1–3 showed good activity against Schistosoma mansoni, with compound 1 showing the best activity against newly transformed schistosomula with 50% activity at 1µM. The isolated compounds were also evaluated for their cytotoxic properties against PC-3 (human prostate adenocarcinoma) and HT-29 (human colorectal adenocarcinoma) cell lines, whereby compounds 2 and 3 showed antiproliferative activity in both cancer cell lines, while compound 1 exhibited antiproliferative activity only on PC-3 cells. With an IC₅₀ value of 43.2 µM, compound 3 was found to be the most active of the 3 investigated compounds. Full article

The association between chemotherapeutic drugs and metal oxide nanoparticles has sparked a rapidly growing interest in cancer nanomedicine. The elaboration of new engineered docetaxel (DTX)-nanocarriers based on titanate nanotubes (TiONts) was reported. The idea was to maintain the drug inside cancer cells and avoid multidrug resistance mechanisms, which often limit drug efficacy by decreasing their intracellular concentrations in tumor cells. HS-PEG_n-COOH (PEG: polyethylene glycol, n = 3000, 5000, 10,000) was conjugated, in an organic medium by covalent linkages, on TiONts surface. This study aimed to investigate the influence of different PEG derivatives chain lengths on the TiONts colloidal stability, on the PEG_n density and conformation, as well as on the DTX biological activity in a prostate cancer model (human PC-3 prostate adenocarcinoma cells). In vitro tests highlighted significant cytotoxicities of the drug after loading DTX on PEG_n-modified TiONts (TiONts-PEG_n-DTX). Higher grafting densities for shorter PEGylated chains were most favorable on DTX cytotoxicity by promoting both colloidal stability in biological media and cells internalization. This promising strategy involves a better understanding of nanohybrid engineering, particularly on the PEGylated chain length influence, and can thus become a potent tool in nanomedicine to fight against cancer. Full article

In this study, we investigated aqueous extracts of three edible mushrooms: Agaricus bisporus (white button mushroom), Pleurotus columbinus (oyster mushroom), and Pleurotus sajor-caju (grey oyster mushroom). The extracts were biochemically characterized for total carbohydrate, phenolic, flavonoid, vitamin, and protein contents besides amino acid analysis. Triple TOF proteome analysis showed 30.1% similarity between proteomes of the two Pleurotus spp. All three extracts showed promising antiviral activities. While Pleurotus columbinus extract showed potent activity against adenovirus (Ad7, selectivity index (SI) = 4.2), Agaricus bisporus showed strong activity against herpes simplex II (HSV-2; SI = 3.7). The extracts showed low cytotoxicity against normal human peripheral blood mononuclear cells (PBMCs) and moderate cytotoxicity against prostate (PC3, DU-145); colorectal (Colo-205); cecum carcinoma (LS-513); liver carcinoma (HepG2); cervical cancer (HeLa); breast adenocarcinoma (MDA-MB-231 and MCF-7) as well as leukemia (CCRF-CEM); acute monocytic leukemia (THP1); acute promyelocytic leukemia (NB4); and lymphoma (U937) cell lines. Antioxidant activity was evaluated using 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging, 2,2′-Azinobis-(3-Ethylbenzthiazolin-6-Sulfonic Acid) ABTS radical cation scavenging, and oxygen radical absorbance capacity (ORAC) assays. The three extracts showed potential antioxidant activities with the maximum activity recorded for Pleurotus columbinus (IC₅₀ µg/mL) = 35.13 ± 3.27 for DPPH, 13.97 ± 4.91 for ABTS, and 29.42 ± 3.21 for ORAC assays. Full article